Skip to main content
SpringerLink
Log in

Discovery and Development of Tumor Angiogenesis Assays

  • Protocol
  • First Online:
Tumor Angiogenesis Assays

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2572))

Abstract

The angiogenesis process was described in its basic concepts in the works of the Scottish surgeon John Hunter and terminologically assessed in the early twentieth century. An aberrant angiogenesis is a prerequisite for cancer cells in solid tumors to grow and metastasize. The sprouting of new blood vessels is one of the major characteristics of cancer and represents a gateway for tumor cells to enter both the blood and lymphatic circulation systems. In vivo, ex vivo, and in vitro models of angiogenesis have provided essential tools for cancer research and antiangiogenic drug screening. Several in vivo studies have been performed to investigate the various steps of tumor angiogenesis and in vitro experiments contributed to dissecting the molecular bases of this phenomenon. Moreover, coculture of cancer and endothelial cells in 2D and 3D matrices have contributed to improve the recapitulation of the complex process of tumor angiogenesis, including the peculiar conditions of tumor microenvironment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lenzi P, Bocci G, Natale G (2016) John Hunter and the origin of the term “angiogenesis”. Angiogenesis 19:255–256. https://doi.org/10.1007/S10456-016-9496-7

    Article  PubMed  Google Scholar 

  2. Natale G, Bocci G, Lenzi P (2017) Looking for the word “angiogenesis” in the history of health sciences: from ancient times to the first decades of the twentieth century. World J Surg 41:1625–1634. https://doi.org/10.1007/S00268-016-3680-1

    Article  PubMed  Google Scholar 

  3. Kretschmer M, Rüdiger D, Zahler S (2021) Mechanical aspects of angiogenesis. Cancers (Basel) 13. https://doi.org/10.3390/CANCERS13194987

  4. Siemann DW (2011) The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by Tumor-Vascular Disrupting Agents. Cancer Treat Rev 37:63–74. https://doi.org/10.1016/J.CTRV.2010.05.001

    Article  CAS  PubMed  Google Scholar 

  5. Natale G, Bocci G (2018) Does metronomic chemotherapy induce tumor angiogenic dormancy? A review of available preclinical and clinical data. Cancer Lett 432:28–37. https://doi.org/10.1016/J.CANLET.2018.06.002

    Article  CAS  PubMed  Google Scholar 

  6. Krishna Priya S, Nagare RP, Sneha VS, Sidhanth C, Bindhya S, Manasa P, Ganesan TS (2016) Tumour angiogenesis-origin of blood vessels. Int J Cancer 139:729–735. https://doi.org/10.1002/IJC.30067

    Article  CAS  PubMed  Google Scholar 

  7. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186. https://doi.org/10.1056/NEJM197111182852108

    Article  CAS  PubMed  Google Scholar 

  8. Oguntade AS, Al-Amodi F, Alrumayh A, Alobaida M, Bwalya M (2021) Anti-angiogenesis in cancer therapeutics: the magic bullet. J Egypt Natl Canc Inst 33. https://doi.org/10.1186/S43046-021-00072-6

  9. Auerbach R, Lewis R, Shinners B, Kubai L, Akhtar N (2003) Angiogenesis assays: a critical overview. Clin Chem 49:32–40. https://doi.org/10.1373/49.1.32

    Article  CAS  PubMed  Google Scholar 

  10. Bhat SM, Badiger VA, Vasishta S, Chakraborty J, Prasad S, Ghosh S, Joshi MB (2021) 3D tumor angiogenesis models: recent advances and challenges. J Cancer Res Clin Oncol 147:3477–3494. https://doi.org/10.1007/s00432-021-03814-0

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hasan J, Shnyder SD, Bibby M, Double JA, Bicknel R, Jayson GC (2004) Quantitative angiogenesis assays in vivo – a review. Angiogenesis 7:1–16. https://doi.org/10.1023/B:AGEN.0000037338.51851.D1

    Article  CAS  PubMed  Google Scholar 

  12. Almalki W, Shahid I, Mehdi A, Hafeez M (2014) Assessment methods for angiogenesis and current approaches for its quantification. Indian J Pharmacol 46:251–256. https://doi.org/10.4103/0253-7613.132152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Staton CA, Reed MWR, Brown NJ (2009) A critical analysis of current in vitro and in vivo angiogenesis assays. Int J Exp Pathol 90:195–221. https://doi.org/10.1111/J.1365-2613.2008.00633.X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Staton CA, Lewis C, Bicknell R (2007) Angiogenesis assays: a critical appraisal of current techniques, Angiogenes Assays A Crit Apprais Curr Technol, pp 1–390. https://doi.org/10.1002/9780470029350

    Book  Google Scholar 

  15. Taraboletti G, Giavazzi R (2004) Modelling approaches for angiogenesis. Eur J Cancer 40:881–889. https://doi.org/10.1016/J.EJCA.2004.01.002

    Article  CAS  PubMed  Google Scholar 

  16. Tufan A, Satiroglu-Tufan N (2005) The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents. Curr Cancer Drug Targets 5:249–266. https://doi.org/10.2174/1568009054064624

    Article  CAS  PubMed  Google Scholar 

  17. Phung MW, Dass CR (2006) In-vitro and in-vivo assays for angiogenesis-modulating drug discovery and development. J Pharm Pharmacol 58:153–160. https://doi.org/10.1211/JPP.58.2.0001

    Article  CAS  PubMed  Google Scholar 

  18. Nambiar DK, Kujur PK, Singh RP (2016) Angiogenesis assays. Methods Mol Biol 1379:107–115. https://doi.org/10.1007/978-1-4939-3191-0_10

    Article  CAS  PubMed  Google Scholar 

  19. Norrby K (2006) In vivo models of angiogenesis. J Cell Mol Med 10:588–612. https://doi.org/10.1111/J.1582-4934.2006.TB00423.X

    Article  CAS  PubMed  Google Scholar 

  20. Nowak-Sliwinska P, Alitalo K, Allen E, Anisimov A, Aplin AC, Auerbach R, Augustin HG, Bates DO, van Beijnum JR, Bender RHF, Bergers G, Bikfalvi A, Bischoff J, Böck BC, Brooks PC, Bussolino F, Cakir B, Carmeliet P, Castranova D, Cimpean AM, Cleaver O, Coukos G, Davis GE, De Palma M, Dimberg A, Dings RPM, Djonov V, Dudley AC, Dufton NP, Fendt SM, Ferrara N, Fruttiger M, Fukumura D, Ghesquière B, Gong Y, Griffin RJ, Harris AL, Hughes CCW, Hultgren NW, Iruela-Arispe ML, Irving M, Jain RK, Kalluri R, Kalucka J, Kerbel RS, Kitajewski J, Klaassen I, Kleinmann HK, Koolwijk P, Kuczynski E, Kwak BR, Marien K, Melero-Martin JM, Munn LL, Nicosia RF, Noel A, Nurro J, Olsson AK, Petrova TV, Pietras K, Pili R, Pollard JW, Post MJ, Quax PHA, Rabinovich GA, Raica M, Randi AM, Ribatti D, Ruegg C, Schlingemann RO, Schulte-Merker S, Smith LEH, Song JW, Stacker SA, Stalin J, Stratman AN, Van de Velde M, van Hinsbergh VWM, Vermeulen PB, Waltenberger J, Weinstein BM, Xin H, Yetkin-Arik B, Yla-Herttuala S, Yoder MC, Griffioen AW (2018) Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis 21:425–532. https://doi.org/10.1007/s10456-018-9613-x

    Article  PubMed  PubMed Central  Google Scholar 

  21. Natale G, Bocci G (2019) Discovery and development of the cardiovascular system with a focus on angiogenesis: a historical overview. Ital J Anat Embryol 124:247–270. https://doi.org/10.13128/IJAE-11656

    Article  Google Scholar 

  22. West JB (2013) Marcello Malpighi and the discovery of the pulmonary capillaries and alveoli. Am J Physiol Lung Cell Mol Physiol 304. https://doi.org/10.1152/AJPLUNG.00016.2013

  23. Schieving JH, Schoenaker MHD, Weemaes CM, van Deuren M, van der Flier M, Seyger MM, Willemsen MAAP (2017) Telangiectasias: small lesions referring to serious disorders. Eur J Paediatr Neurol 21:807–815. https://doi.org/10.1016/J.EJPN.2017.07.016

    Article  CAS  PubMed  Google Scholar 

  24. Ziegler E (1875) Experimentelle Untersuchungen über die Herkunft der Tuberkelelemente, mit besonderer Berücksichtigung der Histogenese der Riesenzellen. Verlag der J. Staudinger’schen Buchhandlung, [S.l.], Würzburg

    Google Scholar 

  25. Maximow A (1902) Experimentelle Untersuchungen über die entzündliche Neubildung von Bindegewebe. Verlag von Gustav Fischer, Jena

    Google Scholar 

  26. Sandison JC (1924) A new method for the microscopic study of living growing tissues by the introduction of a transparent chamber in the rabbit’s ear. Anat Rec 28:281–287. https://doi.org/10.1002/AR.1090280403

    Article  Google Scholar 

  27. Menger M, Laschke M, Vollmar B (2007) Chamber assays. In: Staton C, Lewis C, Bicknell R (eds) Angiogenesis assays. A critical appraisal of current techniques. Wiley, Chichester, pp 239–263

    Google Scholar 

  28. Clark ER, Kirby-Smith HT, Rex RO, Williams RG (1930) Recent modifications in the method of studying living cells and tissues in transparent chambers inserted in the rabbit’s ear. Anat Rec 47:187–211. https://doi.org/10.1002/AR.1090470205

    Article  Google Scholar 

  29. Ide AG, Baker N, Warren SL (1939) Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol 42:891–899

    Google Scholar 

  30. Williams RG (1951) The vascularity of normal and neoplastic grafts in vivo. Cancer Res 11:139–144

    CAS  PubMed  Google Scholar 

  31. Jain RK, Munn LL, Fukumura D (2012) Rabbit ear chambers. Cold Spring Harb Protoc 2012:813–814. https://doi.org/10.1101/PDB.PROT070045

    Article  PubMed  Google Scholar 

  32. Algire GH (1943) An adaptation of the transparent-chamber technique to the mouse. J Natl Cancer Inst 4:1–11. https://doi.org/10.1093/JNCI/4.1.1

    Article  Google Scholar 

  33. Algire GH, Chalkley HW, Legallais FY, Park HD (1945) Vasculae reactions of normal and malignant tissues in vivo. I vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst 6:73–85. https://doi.org/10.1093/JNCI/6.1.73

    Article  Google Scholar 

  34. Papenfuss HD, Gross JF, Intaglietta M, Treese FA (1979) A transparent access chamber for the rat dorsal skin fold. Microvasc Res 18:311–318. https://doi.org/10.1016/0026-2862(79)90039-6

    Article  CAS  PubMed  Google Scholar 

  35. Endrich B, Asaishi K, Götz A, Meßmer K (1980) Technical report – a new chamber technique for microvascular studies in unanesthetized hamsters. Res Exp Med (Berl) 177:125–134. https://doi.org/10.1007/BF01851841

    Article  CAS  Google Scholar 

  36. Lehr HA, Leunig M, Menger MD, Nolte D, Messmer K (1993) Dorsal skinfold chamber technique for intravital microscopy in nude mice. Am J Pathol 143:1055–1062

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Greenblatt M, Shubi P (1968) Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 41:111–124

    CAS  PubMed  Google Scholar 

  38. Yuan F, Salehi HA, Boucher Y, Jain RK, Vasthare US, Tuma RF (1994) Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows. Cancer Res 54:4564–4568

    CAS  PubMed  Google Scholar 

  39. Branemark PI (1959) Vital microscopy of bone marrow in rabbit. Scand J Clin Lab Invest 11(Supp 38):1–82

    PubMed  Google Scholar 

  40. McCuskey RS, McClugage SG, Younker WJ (1971) Microscopy of living bone marrow in situ. Blood 38:87–95. https://doi.org/10.1182/blood.v38.1.87.87

    Article  CAS  PubMed  Google Scholar 

  41. Albrektsson T, Albrektsson B (1978) Microcirculation in grafted bone. A chamber technique for vital microscopy of rabbit bone transplants. Acta Orthop Scand 49:1–7. https://doi.org/10.3109/17453677809005716

    Article  CAS  PubMed  Google Scholar 

  42. Hansen-Algenstaedt N, Schaefer C, Wolfram L, Joscheck C, Schroeder M, Algenstaedt P, Rüther W (2005) Femur window – a new approach to microcirculation of living bone in situ. J Orthop Res 23:1073–1082. https://doi.org/10.1016/J.ORTHRES.2005.02.013

    Article  CAS  PubMed  Google Scholar 

  43. Oikawa T, Sasaki M, Inose M, Shimamura M, Kuboki H, Hirano SI, Kumagai H, Ishizuka M, Takeuchi T (1997) Effects of cytogenin, a novel microbial product, on embryonic and tumor cell-induced angiogenic responses in vivo. Anticancer Res 17:1881–1886

    CAS  PubMed  Google Scholar 

  44. Yonezawa S, Asai T, Oku N (2007) Dorsal airc sac model. In: Staton C, Lewis C, Bicknell R (eds) Angiogenesis assays. A critical appraisal of current techniques. Wiley, Chichester, pp 229–237

    Google Scholar 

  45. Ribatti D, Vacca A, Roncali L, Dammacco F (2000) The chick embryo chorioallantoic membrane as a model for in vivo research on anti-angiogenesis. Curr Pharm Biotechnol 1:73–82. https://doi.org/10.2174/1389201003379040

    Article  CAS  PubMed  Google Scholar 

  46. Richardson M, Singh G (2003) Observations on the use of the avian chorioallantoic membrane (CAM) model in investigations into angiogenesis. Curr Drug Targets Cardiovasc Haematol Disord 3:155–185. https://doi.org/10.2174/1568006033481492

    Article  CAS  PubMed  Google Scholar 

  47. Nowak-Sliwinska P, Segura T, Iruela-Arispe ML (2014) The chicken chorioallantoic membrane model in biology, medicine and bioengineering. Angiogenesis 17:779–804. https://doi.org/10.1007/S10456-014-9440-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Burggren W, Antich MR (2020) Angiogenesis in the avian embryo chorioallantoic membrane: a perspective on research trends and a case study on toxicant vascular effects. J Cardiovasc Dev Dis 7:1–18. https://doi.org/10.3390/JCDD7040056

    Article  Google Scholar 

  49. Chu PY, Koh APF, Antony J, Huang RYJ (2021) Applications of the chick chorioallantoic membrane as an alternative model for cancer studies. Cells Tissues Organs. https://doi.org/10.1159/000513039

  50. Ribatti D (2010) The chick embryo chorioallantoic membrane as an in vivo assay to study antiangiogenesis. Pharmaceuticals (Basel) 3:482–513. https://doi.org/10.3390/PH3030482

    Article  CAS  Google Scholar 

  51. Ribatti D (2016) The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model. Mech Dev 141:70–77. https://doi.org/10.1016/J.MOD.2016.05.003

    Article  CAS  PubMed  Google Scholar 

  52. Ribatti D (2017) The chick embryo chorioallantoic membrane (CAM) assay. Reprod Toxicol 70:97–101. https://doi.org/10.1016/J.REPROTOX.2016.11.004

    Article  CAS  PubMed  Google Scholar 

  53. Ribatti D (2008) Chick embryo chorioallantoic membrane as a useful tool to study angiogenesis. Int Rev Cell Mol Biol 270:181–224. https://doi.org/10.1016/S1937-6448(08)01405-6

    Article  CAS  PubMed  Google Scholar 

  54. Ribatti D (2012) Chicken chorioallantoic membrane angiogenesis model. Methods Mol Biol 843:47–57. https://doi.org/10.1007/978-1-61779-523-7_5

    Article  CAS  PubMed  Google Scholar 

  55. Ribatti D, Gualandris A, Bastaki M, Vacca A, Iurlaro M, Roncali L, Presta M (1997) New model for the study of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane: the gelatin sponge/chorioallantoic membrane assay. J Vasc Res 34:455–463. https://doi.org/10.1159/000159256

    Article  CAS  PubMed  Google Scholar 

  56. Ribatti D, Nico B, Vacca A, Roncali L, Burri PH, Djonov V (2001) Chorioallantoic membrane capillary bed: a useful target for studying angiogenesis and anti-angiogenesis in vivo. Anat Rec 264:317–324. https://doi.org/10.1002/AR.10021

    Article  CAS  PubMed  Google Scholar 

  57. Rous P, Murphy J (1911) Tumor implantations in the developing embryo. J Am Med Assoc LVI:741–742. https://doi.org/10.1001/JAMA.1911.02560100033015

    Article  Google Scholar 

  58. Rous P, Murphy JB (1912) The histological signs of resistance to a transmissible sarcoma of the fowl. J Exp Med 15:270–286. https://doi.org/10.1084/JEM.15.3.270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Murphy JB, Rous P (1912) The behavior of chicken sarcoma implanted in the developing embryo. J Exp Med 15:119–132. https://doi.org/10.1084/JEM.15.2.119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Murphy JB (1912) Transplantability of malignant tumors to the embryos of a foreign species. J Am Med Assoc LIX:874–875. https://doi.org/10.1001/JAMA.1912.04270090118016

    Article  Google Scholar 

  61. Murphy JB (1913) Transplantability of tissues to the embryo of foreign species: its bearing on questions of tissue specificity and tumor immunity. J Exp Med 17:482–498. https://doi.org/10.1084/JEM.17.4.482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ribatti D (2004) The first evidence of the tumor-induced angiogenesis in vivo by using the chorioallantoic membrane assay dated 1913. Leukemia 18:1350–1351. https://doi.org/10.1038/SJ.LEU.2403411

    Article  PubMed  Google Scholar 

  63. Karnofski DA, Ridgway LP, Patterson PA (1952) Tumor transplantation to the chick embryo. Ann N Y Acad Sci 55:313–329. https://doi.org/10.1111/J.1749-6632.1952.TB26547.X

    Article  Google Scholar 

  64. Bender DH, Friedgood CE, Lee HF (1949) Transplantation of heterologous tumors by the intravenous inoculation of the chick embryo. Cancer Res 9:61–64

    CAS  PubMed  Google Scholar 

  65. Dagg CP, Karnofsky DA, Toolan HW, Roddy J (1954) Serial passage of human tumors in chick embryo: growth inhibition by nitrogen mustard. Proc Soc Exp Biol Med 87:223–227. https://doi.org/10.3181/00379727-87-21341

    Article  CAS  PubMed  Google Scholar 

  66. Dagg CP, Karnofsky DA, Roddy J (1956) Growth of transplantable human tumors in the chick embryo and hatched chick. Cancer Res 16:589–594

    CAS  PubMed  Google Scholar 

  67. Ossowski L, Reich E (1980) Experimental model for quantitative study of metastasis. Cancer Res 40:2300–2309

    CAS  PubMed  Google Scholar 

  68. Ausprunk DH, Knighton DR, Folkman J (1974) Differentiation of vascular endothelium in the chick chorioallantois: a structural and autoradiographic study. Dev Biol 38:237–248. https://doi.org/10.1016/0012-1606(74)90004-9

    Article  CAS  PubMed  Google Scholar 

  69. Nguyen M, Shing Y, Folkman J (1994) Quantitation of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane. Microvasc Res 47:31–40. https://doi.org/10.1006/MVRE.1994.1003

    Article  CAS  PubMed  Google Scholar 

  70. Ribatti D, Nico B, Vacca A, Presta M (2006) The gelatin sponge-chorioallantoic membrane assay. Nat Protoc 1:85–91. https://doi.org/10.1038/NPROT.2006.13

    Article  CAS  PubMed  Google Scholar 

  71. Ribatti D, Annese T, Tamma R (2020) The use of the chick embryo CAM assay in the study of angiogenic activiy of biomaterials. Microvasc Res 131. https://doi.org/10.1016/J.MVR.2020.104026

  72. Ribatti D (2021) Two new applications in the study of angiogenesis the CAM assay: acellular scaffolds and organoids. Microvasc Res 140:104304. https://doi.org/10.1016/J.MVR.2021.104304

    Article  PubMed  Google Scholar 

  73. Ny A, Autiero M, Carmeliet P (2006) Zebrafish and Xenopus tadpoles: small animal models to study angiogenesis and lymphangiogenesis. Exp Cell Res 312:684–693. https://doi.org/10.1016/J.YEXCR.2005.10.018

    Article  CAS  PubMed  Google Scholar 

  74. Tobia C, de Sena G, Presta M (2011) Zebrafish embryo, a tool to study tumor angiogenesis. Int J Dev Biol 55:505–509. https://doi.org/10.1387/IJDB.103238CT

    Article  CAS  PubMed  Google Scholar 

  75. Creaser CW (1934) The technic of handling the zebra fish (brachydanio rerio) for the production of eggs which are favorable for embryological research and are available at any specified time throughout the year. Copeia 1934:159. https://doi.org/10.2307/1435845

    Article  Google Scholar 

  76. Varga M (2018) The doctor of delayed publications: the remarkable life of George Streisinger (1927–1984). Zebrafish 15:314–319. https://doi.org/10.1089/ZEB.2017.1531

    Article  PubMed  Google Scholar 

  77. Serbedzija GN, Flynn E, Willett CE (1999) Zebrafish angiogenesis: a new model for drug screening. Angiogenesis 3:353–359. https://doi.org/10.1023/A:1026598300052

    Article  CAS  PubMed  Google Scholar 

  78. Schuermann A, Helker CSM, Herzog W (2014) Angiogenesis in zebrafish. Semin Cell Dev Biol 31:106–114. https://doi.org/10.1016/J.SEMCDB.2014.04.037

    Article  CAS  PubMed  Google Scholar 

  79. Gimbrone MA, Leapman SB, Cotran RS, Folkman J (1973) Tumor angiogenesis: iris neovascularization at a distance from experimental intraocular tumors. J Natl Cancer Inst 50:219–228. https://doi.org/10.1093/JNCI/50.1.219

    Article  PubMed  Google Scholar 

  80. Gimbrone MA, Cotran RS, Leapman SB, Folkman J (1974) Tumor growth and neovascularization: an experimental model using the rabbit cornea. J Natl Cancer Inst 52:413–427. https://doi.org/10.1093/JNCI/52.2.413

    Article  PubMed  Google Scholar 

  81. Shan S, Dewhirst M (2007) Corneal angiogenesis assay. In: Staton C, Lewis CRB (eds) Angiogenesis assays. A critical appraisal of current techniques. Wiley, Chichester, pp 203–222

    Google Scholar 

  82. Morbidelli L, Ciccone V, Ziche M (2021) Studying angiogenesis in the rabbit corneal pocket assay. Methods Mol Biol 2206:89–101. https://doi.org/10.1007/978-1-0716-0916-3_8

    Article  CAS  PubMed  Google Scholar 

  83. Norrby K, Jakobsson A, Sörbo J (1986) Mast-cell-mediated angiogenesis: a novel experimental model using the rat mesentery. Virchows Arch B Cell Pathol Incl Mol Pathol 52:195–206. https://doi.org/10.1007/BF02889963

    Article  CAS  PubMed  Google Scholar 

  84. Bocci G, Danesi R, Benelli U, Innocenti F, Di Paolo A, Fogli S, Del Tacca M (1999) Inhibitory effect of suramin in rat models of angiogenesis in vitro and in vivo. Cancer Chemother Pharmacol 43:205–212. https://doi.org/10.1007/S002800050885

    Article  CAS  PubMed  Google Scholar 

  85. Danesi R, Agen C, Benelli U, Di Paolo A, Nardini D, Bocci G, Basolo F, Campagni A, Del Tacca M (1997) Inhibition of experimental angiogenesis by the somatostatin analogue octreotide acetate (SMS 201-995). Clin Cancer Res 3:265–272

    CAS  PubMed  Google Scholar 

  86. Edwards RH, Sarmenta SS, Hass GM (1960) Stimulation of granulation tissue growth by tissue extracts. Study in intramuscular wounds in rabbits. Arch Pathol 69:286–302

    CAS  PubMed  Google Scholar 

  87. Andrade SP, Fan TP, Lewis GP (1987) Quantitative in-vivo studies on angiogenesis in a rat sponge model. Br J Exp Pathol 68:755–766

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Thiede K, Momburg F, Zangemeister U, Schlag P, Schirrmacher V (1988) Growth and metastasis of human tumors in nude mice following tumor-cell inoculation into a vascularized polyurethane sponge matrix. Int J Cancer 42:939–945. https://doi.org/10.1002/IJC.2910420625

    Article  CAS  PubMed  Google Scholar 

  89. Gospodarowicz D, Ill C (1980) Extracellular matrix and control of proliferation of vascular endothelial cells. J Clin Invest 65:1351–1364. https://doi.org/10.1172/JCI109799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Passaniti A, Kleinman HK, Martin GR (2021) Matrigel: history/background, uses, and future applications. J Cell Commun Signal. https://doi.org/10.1007/S12079-021-00643-1

  91. Passaniti A, Taylor RM, Pili R, Guo Y, Long PV, Haney JA, Pauly RR, Grant DS, Martin GR (1992) A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Investig 67:519–528

    CAS  PubMed  Google Scholar 

  92. Kubota Y, Kleinman HK, Martin GR, Lawley TJ (1988) Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures. J Cell Biol 107:1589–1598. https://doi.org/10.1083/JCB.107.4.1589

    Article  CAS  PubMed  Google Scholar 

  93. Akhtar N, Dickerson EB, Auerbach R (2002) The sponge/matrigel angiogenesis assay. Angiogenesis 5:75–80. https://doi.org/10.1023/A:1021507031486

    Article  CAS  PubMed  Google Scholar 

  94. Guedez L, Rivera AM, Salloum R, Miller ML, Diegmueller JJ, Bungay PM, Stetler-Stevenson WG (2003) Quantitative assessment of angiogenic responses by the directed in vivo angiogenesis assay. Am J Pathol 162:1431–1439. https://doi.org/10.1016/S0002-9440(10)64276-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Fajardo LF, Kowalski J, Kwan HH, Prionas SD, Allison AC (1988) The disc angiogenesis system. Lab Investig 58:718–724

    CAS  PubMed  Google Scholar 

  96. Hanahan D (1985) Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 315:115–122. https://doi.org/10.1038/315115A0

    Article  CAS  PubMed  Google Scholar 

  97. Hanahan D, Christofori G, Naik P, Arbeit J (1996) Transgenic mouse models of tumour angiogenesis: the angiogenic switch, its molecular controls, and prospects for preclinical therapeutic models. Eur J Cancer 32A:2386–2393. https://doi.org/10.1016/S0959-8049(96)00401-7

    Article  CAS  PubMed  Google Scholar 

  98. Bergers G, Javaherian K, Lo KM, Folkman J, Hanahan D (1999) Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 284:808–812. https://doi.org/10.1126/SCIENCE.284.5415.808

    Article  CAS  PubMed  Google Scholar 

  99. Casanovas O, Hicklin DJ, Bergers G, Hanahan D (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8:299–309. https://doi.org/10.1016/J.CCR.2005.09.005

    Article  CAS  PubMed  Google Scholar 

  100. Guy CT, Cardiff RD, Muller WJ (1992) Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 12:954–961. https://doi.org/10.1128/MCB.12.3.954-961.1992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lin EY, Jones JG, Li P, Zhu L, Whitney KD, Muller WJ, Pollard JW (2003) Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am J Pathol 163:2113–2126. https://doi.org/10.1016/S0002-9440(10)63568-7

    Article  PubMed  PubMed Central  Google Scholar 

  102. Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW (2006) Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66:11238–11246. https://doi.org/10.1158/0008-5472.CAN-06-1278

    Article  CAS  PubMed  Google Scholar 

  103. Eklund L, Bry M, Alitalo K (2013) Mouse models for studying angiogenesis and lymphangiogenesis in cancer. Mol Oncol 7:259–282. https://doi.org/10.1016/J.MOLONC.2013.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G (1992) Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84:1875–1887. https://doi.org/10.1093/jnci/84.24.1875

    Article  CAS  PubMed  Google Scholar 

  105. Konerding MA, Steinberg F (1989) Scanning and transmission electron microscopic studies on the vascular system of xenotransplanted human tumors on nude mice. Prog Clin Biol Res 295:475–480

    CAS  PubMed  Google Scholar 

  106. Konerding MA, Steinberg F, Streffer C (1989) The vasculature of xenotransplanted human melanomas and sarcomas on nude mice. I Vascular corrosion casting studies. Acta Anat (Basel) 136:21–26. https://doi.org/10.1159/000146792

    Article  CAS  Google Scholar 

  107. Goertz DE, Yu JL, Kerbel RS, Burns PN, Foster FS (2002) High-frequency Doppler ultrasound monitors the effects of antivascular therapy on tumor blood flow. Cancer Res 62:6371–6375

    CAS  PubMed  Google Scholar 

  108. Sherar MD, Noss MB, Foster FS (1987) Ultrasound backscatter microscopy images the internal structure of living tumour spheroids. Nature 330:493–495. https://doi.org/10.1038/330493A0

    Article  CAS  PubMed  Google Scholar 

  109. Keyes KA, Mann L, Teicher B, Alvarez E (2003) Site-dependent angiogenic cytokine production in human tumor xenografts. Cytokine 21:98–104. https://doi.org/10.1016/S1043-4666(03)00015-2

    Article  CAS  PubMed  Google Scholar 

  110. Yang M, Baranov E, Li XM, Wang JW, Jiang P, Li N, Moossa AR, Penman S, Hoffman RM (2001) Whole-body and intravital optical imaging of angiogenesis in orthotopically implanted tumors. Proc Natl Acad Sci U S A 98:2616–2621. https://doi.org/10.1073/PNAS.051626698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Rofstad EK (1994) Orthotopic human melanoma xenograft model systems for studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern. Br J Cancer 70:804–812. https://doi.org/10.1038/BJC.1994.403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Loi M, di Paolo D, Becherini P, Zorzoli A, Perri P, Carosio R, Cilli M, Ribatti D, Brignole C, Pagnan G, Ponzoni M, Pastorino F (2011) The use of the orthotopic model to validate antivascular therapies for cancer. Int J Dev Biol 55:547–555. https://doi.org/10.1387/IJDB.103230ML

    Article  CAS  PubMed  Google Scholar 

  113. Hoffman RM (2004) Imaging tumor angiogenesis with fluorescent proteins. APMIS 112:441–449. https://doi.org/10.1111/J.1600-0463.2004.APM11207-0806.X

    Article  PubMed  Google Scholar 

  114. Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52:2745–2756. https://doi.org/10.1172/JCI107470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Nachman RL, Jaffe EA (2004) Endothelial cell culture: beginnings of modern vascular biology. J Clin Invest 114:1037–1040. https://doi.org/10.1172/JCI23284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Folkman J, Haudenschild CC, Zetter BR (1979) Long-term culture of capillary endothelial cells. Proc Natl Acad Sci U S A 76:5217–5221. https://doi.org/10.1073/PNAS.76.10.5217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Bouïs D, Hospers GAP, Meijer C, Molema G, Mulder NH (2001) Endothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis 4:91–102. https://doi.org/10.1023/A:1012259529167

    Article  PubMed  Google Scholar 

  118. Gimbrone MA, Fareed GC (1976) Transformation of cultured human vascular endothelium by SV40 DNA. Cell 9:685–693. https://doi.org/10.1016/0092-8674(76)90132-X

    Article  PubMed  Google Scholar 

  119. Edgell CJS, McDonald CC, Graham JB (1983) Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci U S A 80:3734–3737. https://doi.org/10.1073/PNAS.80.12.3734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ (1992) HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol 99:683–690. https://doi.org/10.1111/1523-1747.EP12613748

    Article  CAS  PubMed  Google Scholar 

  121. Folkman J, Haudenschild C (1980) Angiogenesis in vitro. Nature 288:551–556. https://doi.org/10.1038/288551A0

    Article  CAS  PubMed  Google Scholar 

  122. Lee W-S (2007) Endothelial cell proliferation assays. In: Staton CA, Lewis C, Bicknell R (eds) Angiogenesis assays. A critical appraisal of current techniques. Wiley, Chichester, pp 39–50

    Google Scholar 

  123. Combs JW, Lagunoff D, Benditt EP (1965) Differentiation and proliferation of embryonic mast cells of the rat. J Cell Biol 25:577–592. https://doi.org/10.1083/JCB.25.3.577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Hsu HK, Juan SH, Ho PY, Liang YC, Lin CH, Teng CM, Sen LW (2003) YC-1 inhibits proliferation of human vascular endothelial cells through a cyclic GMP-independent pathway. Biochem Pharmacol 66:263–271. https://doi.org/10.1016/S0006-2952(03)00244-2

    Article  CAS  PubMed  Google Scholar 

  125. Bocci G, Nicolaou KC, Kerbel RS (2002) Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. Cancer Res 62:6938–6943

    CAS  PubMed  Google Scholar 

  126. Dolbeare F, Gratzner H, Pallavicini MG, Gray JW (1983) Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine. Proc Natl Acad Sci U S A 80:5573–5577. https://doi.org/10.1073/PNAS.80.18.5573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Li Y, Chang Y, Ye N, Dai D, Chen Y, Zhang N, Sun G, Sun Y (2017) Advanced glycation end products inhibit the proliferation of human umbilical vein endothelial cells by inhibiting cathepsin D. Int J Mol Sci:18. https://doi.org/10.3390/IJMS18020436

  128. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  129. Weiss A, Ding X, van Beijnum JR, Wong I, Wong TJ, Berndsen RH, Dormond O, Dallinga M, Shen L, Schlingemann RO, Pili R, Ho CM, Dyson PJ, van den Bergh H, Griffioen AW, Nowak-Sliwinska P (2015) Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer. Angiogenesis 18:233–244. https://doi.org/10.1007/S10456-015-9462-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Polytarchou C, Hatziapostolou M, Papadimitriou E (2007) Endothelial cell migration assays. In: Staton CA, Lewis C, Bicknell R (eds) Angiogenesis assays. A critical appraisal of current techniques. Wiley, Chichester, pp 51–64

    Google Scholar 

  131. Boyden S (1962) The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med 115:453–466. https://doi.org/10.1084/JEM.115.3.453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Falk W, Goodwin RH, Leonard EJ (1980) A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration. J Immunol Methods 33:239–247. https://doi.org/10.1016/0022-1759(80)90211-2

    Article  CAS  PubMed  Google Scholar 

  133. Taraboletti G, Roberts D, Liotta LA, Giavazzi R (1990) Platelet thrombospondin modulates endothelial cell adhesion, motility, and growth: a potential angiogenesis regulatory factor. J Cell Biol 111:765–772. https://doi.org/10.1083/JCB.111.2.765

    Article  CAS  PubMed  Google Scholar 

  134. Taraboletti G, Belotti D, Dejana E, Mantovani A, Giavazzi R (1993) Endothelial cell migration and invasiveness are induced by a soluble factor produced by murine endothelioma cells transformed by polyoma virus middle T oncogene. Cancer Res 53:3812–3816

    CAS  PubMed  Google Scholar 

  135. Lampugnani MG (1999) Cell migration into a wounded area in vitro. Methods Mol Biol 96:177–182. https://doi.org/10.1385/1-59259-258-9:177

    Article  CAS  PubMed  Google Scholar 

  136. Wong MKK, Gotlieb AI (1984) In vitro reendothelialization of a single-cell wound. Role of microfilament bundles in rapid lamellipodia-mediated wound closure. Lab Investig 51:75–81

    CAS  PubMed  Google Scholar 

  137. Wong MKK, Gotlieb AI (1988) The reorganization of microfilaments, centrosomes, and microtubules during in vitro small wound reendothelialization. J Cell Biol 107:1777–1783. https://doi.org/10.1083/JCB.107.5.1777

    Article  CAS  PubMed  Google Scholar 

  138. Auerbach R, Auerbach W, Polakowski I (1991) Assays for angiogenesis: a review. Pharmacol Ther 51:1–11. https://doi.org/10.1016/0163-7258(91)90038-N

    Article  PubMed  Google Scholar 

  139. Yarrow JC, Perlman ZE, Westwood NJ, Mitchison TJ (2004) A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods. BMC Biotechnol 4. https://doi.org/10.1186/1472-6750-4-21

  140. Pratt BM, Harris AS, Morrow JS, Madri JA (1984) Mechanisms of cytoskeletal regulation. Modulation of aortic endothelial cell spectrin by the extracellular matrix. Am J Pathol 117:349–354

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Kohama Y, Oka H, Murayama N, Iida K, Itoh M, Itoh M, Ying X, Mimura T (1992) Increase of migration of cultured endothelial cells by angiotensin-converting enzyme inhibitor derived from tuna muscle. J Pharmacobiodyn 15:223–229. https://doi.org/10.1248/BPB1978.15.223

    Article  CAS  PubMed  Google Scholar 

  142. Cai G, Lian J, Shapiro SS, Beacham DA (2000) Evaluation of endothelial cell migration with a novel in vitro assay system. Methods Cell Sci 22:107–114. https://doi.org/10.1023/A:1009864613566

    Article  CAS  PubMed  Google Scholar 

  143. Albrecht-Buehler G (1977) The phagokinetic tracks of 3T3 cells. Cell 11:395–404. https://doi.org/10.1016/0092-8674(77)90057-5

    Article  CAS  PubMed  Google Scholar 

  144. Zetter BR (1980) Migration of capillary endothelial cells is stimulated by tumour-derived factors. Nature 285:41–43. https://doi.org/10.1038/285041A0

    Article  CAS  PubMed  Google Scholar 

  145. Obeso JL, Auerbach R (1984) A new microtechnique for quantitating cell movement in vitro using polystyrene bead monolayers. J Immunol Methods 70:141–152. https://doi.org/10.1016/0022-1759(84)90180-7

    Article  CAS  PubMed  Google Scholar 

  146. Svensson CM, Medyukhina A, Belyaev I, Al-Zaben N, Figge MT (2018) Untangling cell tracks: quantifying cell migration by time lapse image data analysis. Cytometry A 93:357–370. https://doi.org/10.1002/CYTO.A.23249

    Article  PubMed  Google Scholar 

  147. Smith E, Staton CA (2007) Tubule formation assays. In: Staton CA, Lewis C, Bicknell R (eds) Angiogenesis assays. A critical appraisal of current techniques. Wiley, Chichester, pp 65–87

    Google Scholar 

  148. Maciag T, Kadish J, Wllkins L, Stemerman MB, Weinstein R (1982) Organizational behavior of human umbilical vein endothelial cells. J Cell Biol 94:511–520. https://doi.org/10.1083/JCB.94.3.511

    Article  CAS  PubMed  Google Scholar 

  149. Lawley TJ, Kubota Y (1989) Induction of morphologic differentiation of endothelial cells in culture. J Invest Dermatol 93:59S–61S. https://doi.org/10.1111/1523-1747.EP12581070

    Article  CAS  PubMed  Google Scholar 

  150. Grant DS, Lelkes PI, Fukuda K, Kleinman HK (1991) Intracellular mechanisms involved in basement membrane induced blood vessel differentiation in vitro. In Vitro Cell Dev Biol 27A:327–336. https://doi.org/10.1007/BF02630910

    Article  CAS  PubMed  Google Scholar 

  151. Connolly JO, Simpson N, Hewlett L, Hall A (2002) Rac regulates endothelial morphogenesis and capillary assembly. Mol Biol Cell 13:2474–2485. https://doi.org/10.1091/MBC.E02-01-0006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Montesano R, Orci L, Vassalli P (1983) In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices. J Cell Biol 97:1648–1652. https://doi.org/10.1083/JCB.97.5.1648

    Article  CAS  PubMed  Google Scholar 

  153. Madri JA, Williams SK (1983) Capillary endothelial cell cultures: phenotypic modulation by matrix components. J Cell Biol 97:153–165. https://doi.org/10.1083/JCB.97.1.153

    Article  CAS  PubMed  Google Scholar 

  154. Vailhé B, Lecomte M, Wiernsperger N, Tranqui L (1998) The formation of tubular structures by endothelial cells is under the control of fibrinolysis and mechanical factors. Angiogenesis 2:331–344. https://doi.org/10.1023/A:1009238717101

    Article  PubMed  Google Scholar 

  155. Sanz L, Pascual M, Muñoz A, González MA, Salvador CH, Álvarez-Vallina L (2002) Development of a computer-assisted high-throughput screening platform for anti-angiogenic testing. Microvasc Res 63:335–339. https://doi.org/10.1006/MVRE.2001.2389

    Article  CAS  PubMed  Google Scholar 

  156. Nehls V, Drenckhahn D (1995) A novel, microcarrier-based in vitro assay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis. Microvasc Res 50:311–322. https://doi.org/10.1006/MVRE.1995.1061

    Article  CAS  PubMed  Google Scholar 

  157. Gagnon E, Cattaruzzi P, Griffith M, Muzakare L, LeFlaol K, Faure R, Béliveau R, Hussain SN, Koutsilieris M, Doillon CJ (2002) Human vascular endothelial cells with extended life spans: in vitro cell response, protein expression, and angiogenesis. Angiogenesis 5:21–33. https://doi.org/10.1023/A:1021573013503

    Article  CAS  PubMed  Google Scholar 

  158. Ilan N, Mahooti S, Madri JA (1998) Distinct signal transduction pathways are utilized during the tube formation and survival phases of in vitro angiogenesis. J Cell Sci 111(Pt 2):3621–3631

    Article  CAS  PubMed  Google Scholar 

  159. Chau C, Figg WD (2007) Whole or patial vessel outgrowth assays. In: Staton CA, Lewis C, Bicknell R (eds) Angiogenesis assays. A critical appraisal of current techniques. Wiley, Chichester, pp 106–121

    Google Scholar 

  160. Nicosia RF, Ottinetti A (1990) Growth of microvessels in serum-free matrix culture of rat aorta. A quantitative assay of angiogenesis in vitro. Lab Investig 63:115–122

    CAS  PubMed  Google Scholar 

  161. Bonanno E, Iurlaro M, Madri JA, Nicosia RF (2000) Type IV collagen modulates angiogenesis and neovessel survival in the rat aorta model. In Vitro Cell Dev Biol Anim 36:336–340. https://doi.org/10.1290/1071-2690(2000)036<0336:TICMAA>2.0.CO;2

    Article  CAS  PubMed  Google Scholar 

  162. Nicosia RF, Ottinetti A (1990) Modulation of microvascular growth and morphogenesis by reconstituted basement membrane gel in three-dimensional cultures of rat aorta: a comparative study of angiogenesis in matrigel, collagen, fibrin, and plasma clot. In Vitro Cell Dev Biol 26:119–128. https://doi.org/10.1007/BF02624102

    Article  CAS  PubMed  Google Scholar 

  163. Kruger EA, Duray PH, Tsokos MG, Venzon DJ, Libutti SK, Dixon SC, Rudek MA, Pluda J, Allegra C, Figg WD (2000) Endostatin inhibits microvessel formation in the ex vivo rat aortic ring angiogenesis assay. Biochem Biophys Res Commun 268:183–191. https://doi.org/10.1006/BBRC.1999.2018

    Article  CAS  PubMed  Google Scholar 

  164. Blatt RJ, Clark AN, Courtney J, Tully C, Tucker AL (2004) Automated quantitative analysis of angiogenesis in the rat aorta model using Image-Pro Plus 4.1. Comput Methods Prog Biomed 75:75–79. https://doi.org/10.1016/J.CMPB.2003.11.001

    Article  Google Scholar 

  165. Aplin AC, Nicosia RF (2016) The aortic ring assay and its use for the study of tumor angiogenesis. Methods Mol Biol 1464:63–72. https://doi.org/10.1007/978-1-4939-3999-2_6

    Article  CAS  PubMed  Google Scholar 

  166. Aplin AC, Nicosia RF (2019) The plaque-aortic ring assay: a new method to study human atherosclerosis-induced angiogenesis. Angiogenesis 22:421–431. https://doi.org/10.1007/S10456-019-09667-Z

    Article  CAS  PubMed  Google Scholar 

  167. McDonald DM, Teicher BA, Stetler-Stevenson W, SSW N, Figg WD, Folkman J, Hanahan D, Auerbach R, O’Reilly M, Herbst R, Cheresh D, Gordon M, Eggermont A, Libutti SK (2004) Report from the society for biological therapy and vascular biology faculty of the NCI workshop on angiogenesis monitoring. J Immunother 27:161–175. https://doi.org/10.1097/00002371-200403000-00010

    Article  PubMed  Google Scholar 

  168. Akimoto T, Liapis H, Hammerman MR (2002) Microvessel formation from mouse embryonic aortic explants is oxygen and VEGF dependent. Am J Physiol Regul Integr Comp Physiol 283. https://doi.org/10.1152/AJPREGU.00699.2001

  169. Zhu WH, Iurlaro M, MacIntyre A, Fogel E, Nicosia RF (2003) The mouse aorta model: influence of genetic background and aging on bFGF- and VEGF-induced angiogenic sprouting. Angiogenesis 6:193–199. https://doi.org/10.1023/B:AGEN.0000021397.18713.9C

    Article  CAS  PubMed  Google Scholar 

  170. Muthukkaruppan V, Shinners B, Lewis R, Park S-J, Baechler B, Auerbach R (2000) The chick embryo aortic arch assay: a new, rapid, quantifiable in vitro method for testing the efficacy of angiogenic and anti-angiogenic factors in a three-dimensional, serum-free organ culture system. Proc Am Assoc Cancer Res 41:65

    Google Scholar 

  171. Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM (2002) Hsp 90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem 277:29936–29944. https://doi.org/10.1074/JBC.M204733200

    Article  CAS  PubMed  Google Scholar 

  172. Stiffey-Wilusz J, Boice JA, Ronan J, Fletcher AM, Anderson MS (2001) An ex vivo angiogenesis assay utilizing commercial porcine carotid artery: modification of the rat aortic ring assay. Angiogenesis 4:3–9. https://doi.org/10.1023/A:1016604327305

    Article  CAS  PubMed  Google Scholar 

  173. Brown KJ, Maynes SF, Bezos A, Maguire DJ, Ford MD, Parish CR (1996) A novel in vitro assay for human angiogenesis. Lab Investig 75:539–555

    CAS  PubMed  Google Scholar 

  174. Bocci G, Fasciani A, Danesi R, Viacava P, Genazzani AR, Del Tacca M (2001) In-vitro evidence of autocrine secretion of vascular endothelial growth factor by endothelial cells from human placental blood vessels. Mol Hum Reprod 7:771–777. https://doi.org/10.1093/MOLEHR/7.8.771

    Article  CAS  PubMed  Google Scholar 

  175. Bocci G, Culler MD, Fioravanti A, Orlandi P, Fasciani A, Colucci R, Taylor JE, Sadat D, Danesi R, Del Tacca M (2007) In vitro antiangiogenic activity of selective somatostatin subtype-1 receptor agonists. Eur J Clin Investig 37:700–708. https://doi.org/10.1111/J.1365-2362.2007.01848.X

    Article  CAS  Google Scholar 

  176. Jung SP, Siegrist B, Wade MR, Anthony CT, Woltering EA (2001) Inhibition of human angiogenesis with heparin and hydrocortisone. Angiogenesis 4:175–185. https://doi.org/10.1023/A:1014089706107

    Article  CAS  PubMed  Google Scholar 

  177. Kruger EA, Duray PH, Price DK, Pluda JM, Figg WD (2001) Approaches to preclinical screening of antiangiogenic agents. Semin Oncol 28:570–576. https://doi.org/10.1016/S0093-7754(01)90026-0

    Article  CAS  PubMed  Google Scholar 

  178. Price DK, Ando Y, Kruger EA, Weiss M, Figg WD (2002) 5′-OH-thalidomide, a metabolite of thalidomide, inhibits angiogenesis. Ther Drug Monit 24:104–110. https://doi.org/10.1097/00007691-200202000-00017

    Article  CAS  PubMed  Google Scholar 

  179. Macpherson GR, Ng SSW, Forbes SL, Melillo G, Karpova T, McNally J, Conrads TP, Veenstra TD, Martinez A, Cuttitta F, Price DK, Figg WD (2003) Anti-angiogenic activity of human endostatin is HIF-1-independent in vitro and sensitive to timing of treatment in a human saphenous vein assay. Mol Cancer Ther 2:845–854

    CAS  PubMed  Google Scholar 

  180. Kramer RH, Nicolson GL (1979) Interactions of tumor cells with vascular endothelial cell monolayers: a model for metastatic invasion. Proc Natl Acad Sci U S A 76:5704–5708. https://doi.org/10.1073/PNAS.76.11.5704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Nicolson GL (1982) Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem 30:214–220. https://doi.org/10.1177/30.3.7061823

    Article  CAS  PubMed  Google Scholar 

  182. Khodarev NN, Yu J, Labay E, Darga T, Brown CK, Mauceri HJ, Yassari R, Gupta N, Weichselbaum RR (2003) Tumour-endothelium interactions in co-culture: coordinated changes of gene expression profiles and phenotypic properties of endothelial cells. J Cell Sci 116:1013–1022. https://doi.org/10.1242/JCS.00281

    Article  CAS  PubMed  Google Scholar 

  183. Knüchel R, Hofstddter F, Feichtinger J, Recktenwald A, Franke RP, Hollweg H, Rübben H, Rammel E, Jakse G (1987) Multicellular bladder tumor spheroids in coculture with human endothelial cell monolayers. Urol Int 42:176–180. https://doi.org/10.1159/000281890

    Article  PubMed  Google Scholar 

  184. Yuhas JM, Li AP, Martinez AO, Ladman AJ (1977) A simplified method for production and growth of multicellular tumor spheroids. Cancer Res 37:3639–3643

    CAS  PubMed  Google Scholar 

  185. Knuchel R, Feichtinger J, Recktenwald A, Hollweg HG, Franke P, Jakse G, Rammal E, Hofstadter F (1988) Interactions between bladder tumor cells as tumor spheroids from the cell line J82 and human endothelial cells in vitro. J Urol 139:640–645. https://doi.org/10.1016/S0022-5347(17)42550-X

    Article  CAS  PubMed  Google Scholar 

  186. Wartenberg M, Finkensieper A, Hescheler J, Sauer H (2006) Confrontation cultures of embryonic stem cells with multicellular tumor spheroids to study tumor-induced angiogenesis. In: Turksen K (ed) Methods in molecular biology. Human Press, Clifton, pp 313–328

    Google Scholar 

  187. Ghosh S, Joshi MB, Ivanov D, Feder-Mengus C, Spagnoli GC, Martin I, Erne P, Resink TJ (2007) Use of multicellular tumor spheroids to dissect endothelial cell–tumor cell interactions: a role for T-cadherin in tumor angiogenesis. FEBS Lett 581:4523–4528. https://doi.org/10.1016/J.FEBSLET.2007.08.038

    Article  CAS  PubMed  Google Scholar 

  188. Ehsan SM, Welch-Reardon KM, Waterman ML, CCW H, George SC (2014) A three-dimensional in vitro model of tumor cell intravasation. Integr Biol 6:603–610. https://doi.org/10.1039/C3IB40170G

    Article  CAS  Google Scholar 

  189. Lazzari G, Nicolas V, Matsusaki M, Akashi M, Couvreur P, Mura S (2018) Multicellular spheroid based on a triple co-culture: a novel 3D model to mimic pancreatic tumor complexity. Acta Biomater 78:296–307. https://doi.org/10.1016/J.ACTBIO.2018.08.008

    Article  CAS  PubMed  Google Scholar 

  190. Bray LJ, Binner M, Holzheu A, Friedrichs J, Freudenberg U, Hutmacher DW, Werner C (2015) Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis. Biomaterials 53:609–620. https://doi.org/10.1016/J.BIOMATERIALS.2015.02.124

    Article  CAS  PubMed  Google Scholar 

  191. DelNero P, Lane M, Verbridge SS, Kwee B, Kermani P, Hempstead B, Stroock A, Fischbach C (2015) 3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways. Biomaterials 55:110–118. https://doi.org/10.1016/J.BIOMATERIALS.2015.03.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Meng F, Meyer CM, Joung D, Vallera DA, MC MA, Panoskaltsis-Mortari A (2019) 3D bioprinted in vitro metastatic models via reconstruction of tumor microenvironments. Adv Mater 31:1806899. https://doi.org/10.1002/ADMA.201806899

    Article  Google Scholar 

  193. Wang Y, Takeishi K, Li Z, Cervantes-Alvarez E, de L’Hortet LC, Guzman-Lepe J, Cui X, Zhu J (2017) Microenvironment of a tumor-organoid system enhances hepatocellular carcinoma malignancy-related hallmarks. 13:83–94. https://doi.org/10.1080/15476278.2017.1322243

  194. Shirure VS, Bi Y, Curtis MB, Lezia A, Goedegebuure MM, Goedegebuure SP, Aft R, Fields RC, George SC (2018) Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids. Lab Chip 18:3687–3702. https://doi.org/10.1039/C8LC00596F

    Article  CAS  PubMed  Google Scholar 

  195. Mazio C, Casale C, Imparato G, Urciuolo F, Netti PA (2018) Recapitulating spatiotemporal tumor heterogeneity in vitro through engineered breast cancer microtissues. Acta Biomater 73:236–249. https://doi.org/10.1016/J.ACTBIO.2018.04.028

    Article  PubMed  Google Scholar 

  196. Sobrino A, Phan DTT, Datta R, Wang X, Hachey SJ, Romero-López M, Gratton E, Lee AP, George SC, CCW H (2016) 3D microtumors in vitro supported by perfused vascular networks. Sci Reports 6:1–11. https://doi.org/10.1038/srep31589

    Article  CAS  Google Scholar 

  197. Bayat N, Izadpanah R, Ebrahimi-Barough S, Javidan AN, Ai A, MMM A, Saberi H, Ai J (2018) The anti-angiogenic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel: in 3D in vitro model. Asian Pac J Cancer Prev 19:2553–2560. https://doi.org/10.22034/APJCP.2018.19.9.2553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Wörsdörfer P, Dalda N, Kern A, Krüger S, Wagner N, Kwok CK, Henke E, Ergün S (2019) Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells. Sci Rep 9:1–13. https://doi.org/10.1038/s41598-019-52204-7

    Article  CAS  Google Scholar 

  199. Esch EW, Bahinski A, Huh D (2015) Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov 14:248–260. https://doi.org/10.1038/nrd4539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Wang X, Sun Q, Pei J (2018) Microfluidic-based 3D engineered microvascular networks and their applications in vascularized microtumor models. Micromachines 9. https://doi.org/10.3390/mi9100493

  201. Kim S, Lee H, Chung M, Jeon NL (2013) Engineering of functional, perfusable 3D microvascular networks on a chip. Lab Chip 13:1489–1500. https://doi.org/10.1039/C3LC41320A

    Article  CAS  PubMed  Google Scholar 

  202. Chung S, Sudo R, MacK PJ, Wan CR, Vickerman V, Kamm RD (2009) Cell migration into scaffolds under co-culture conditions in a microfluidic platform. Lab Chip 9:269–275. https://doi.org/10.1039/B807585A

    Article  CAS  PubMed  Google Scholar 

  203. Buchanan CF, Verbridge SS, Vlachos PP, Rylander MN (2015) Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model. 8:517–524. https://doi.org/10.4161/19336918.2014.970001

  204. Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD (2012) Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc Natl Acad Sci U S A 109:13515–13520. https://doi.org/10.1073/PNAS.1210182109/-/DCSUPPLEMENTAL

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Mercurio A, Sharples L, Corbo F, Franchini C, Vacca A, Catalano A, Carocci A, Kamm RD, Pavesi A, Adriani G (2019) Phthalimide derivative shows anti-angiogenic activity in a 3D microfluidic model and no teratogenicity in zebrafish embryos. Front Pharmacol 10:349. https://doi.org/10.3389/FPHAR.2019.00349/BIBTEX

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy

    Gianfranco Natale

  2. Museum of Human Anatomy “Filippo Civinini”, School of Medicine, University of Pisa, Pisa, Italy

    Gianfranco Natale

  3. Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Pisa, Italy

    Guido Bocci

Authors
  1. Gianfranco Natale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guido Bocci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guido Bocci .

Editor information

Editors and Affiliations

  1. Department of Basic Medical Sciences, Neurosciences and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy

    Domenico Ribatti

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Natale, G., Bocci, G. (2023). Discovery and Development of Tumor Angiogenesis Assays. In: Ribatti, D. (eds) Tumor Angiogenesis Assays. Methods in Molecular Biology, vol 2572. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2703-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2703-7_1

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2702-0

  • Online ISBN: 978-1-0716-2703-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation