Abstract
Tumor cell metastasis through blood circulation is a complex process and is one of the great challenges in cancer research as metastatic spread is responsible for ∼90% of cancer-related mortality. Tumor cell intravasation into, arrest and adhesion at, and extravasation from the microvessel walls are critical steps in metastatic spread. Understanding these steps may lead to new therapeutic concepts for tumor metastasis. Vascular endothelium forming the microvessel wall and the glycocalyx layer at its surface are the principal barriers to and regulators of the material exchange between circulating blood and body tissues. The cleft between adjacent endothelial cells is the principal pathway for water and solute transport through the microvessel wall in health. Recently, this cleft has been found to be the location for tumor cell adhesion and extravasation. The blood-flow-induced hydrodynamic factors such as shear rates and stresses, shear rate and stress gradients, as well as vorticities, especially at the branches and turns of microvasculatures, also play important roles in tumor cell arrest and adhesion. This chapter therefore reports the current advances from in vivo animal studies and in vitro culture cell studies to demonstrate how the endothelial integrity or microvascular permeability, hydrodynamic factors, microvascular geometry, cell adhesion molecules, and surrounding extracellular matrix affect critical steps of tumor metastasis in the microcirculation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Achen MG, Stacker SA (2008) Molecular control of lymphatic metastasis. Ann N Y Acad Sci 1131:225–234
Adamson RH, Clough G (1992) Plasma proteins modify the endothelial cell glycocalyx of frog mesenteric microvessels. J Physiol 445:473–486
Adamson RH, Lenz JF, Zhang X, Adamson GN, Weinbaum S, Curry FE (2004) Oncotic pressures opposing filtration across non-fenestrated rat microvessels. J Physiol 557:889–907
Arkill KP, Knupp C, Michel CC, Neal CR, Qvortrup K, Rostgaard J, Squire JM (2011) Similar endothelial glycocalyx structures in microvessels from a range of mammalian tissues: evidence for a common filtering mechanism? Biophys J 101:1046–1056
Bacac M, Stamenkovic I (2008) Metastatic cancer cell. Annu Rev Pathol 3:221–247
Bates DO, Heald RI, Curry FE, Williams B (2001) Vascular endothelial growth factor increases Rana vascular permeability and compliance by different signalling pathways. J Physiol 533(Pt. 1):263–272
Berman AT, Thukral AD, Hwang WT, Solin LJ, Vapiwala N (2013) Incidence and patterns of distant metastases for patients with early-stage breast cancer after breast conservation treatment. Clin Breast Cancer 13:88–94
Betteridge KB, Arkill KP, Neal CR, Harper SJ, Foster RR, Satchell SC, Bates DO, Salmon AHJ (2017) Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function. J Physiol 595(15):5015–5035
Brenner W, Langer P, Oesch F, Edgell CJ, Wieser RJ (1995) Tumor cell-endothelium adhesion in an artificial venule. Anal Biochem 225:213–219
Bucci M, Roviezzo F, Posadas I, Yu J, Parente L (2005) Endothelial nitric oxide synthase activation is critical for vascular leakage during acute inflammation in vivo. Proc Natl Acad Sci U S A 102:904–908
Bundgaard M (1984) The three-dimensional organization of tight junctions in a capillary endothelium revealed by serial-section electron microscopy. J Ultmstruct Res 88:1–17
Cai B, Fan J, Zeng M, Zhang L, Fu BM (2012) Adhesion of malignant mammary tumor cell MDA-MB-231 to microvessel wall increases microvascular permeability via degradation of endothelial surface glycocalyx. J of Appl Physiol 13(7):1141–1153
Cancel LM, Fitting A, Tarbell JM (2007) In vitro study of LDL transport under pressurized (convective) conditions. Am J Phys 293:H126–H132
CDC Report (2015) Number of deaths for leading causes of death
Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572
Chen MB, Whisler JA, Jeon JS, Kamm RD (2013) Mechanisms of tumor cell extravasation in an in vitro microvascular network platform. Integr Biol (Camb) 5:1262–1271
Chen MB, Whisler JA, Fröse J, Yu C, Shin Y, Kamm RD (2017) On-chip human microvasculature assay for visualization and quantification of tumor cell extravasation dynamics. Nat Protoc 12(5):865–880
Chi CW, Rezwanuddin Ahmed AH, Dereli-Korkut Z, Wang S (2016) Microfluidic cell chips for high throughput drug screening. Bioanalysis 8(9):921–937
Chiu JJ, Chen LJ, Lee PL, Lee CI, Lo LW (2003) Shear stress inhibits adhesion molecule expression in vascular endothelial cells induced by coculture with smooth muscle cells. Blood 101:2667–2674
Chotard-Ghodsnia R, Haddad O, Leyrat A, Drochon A, Verdier C, Duperray A (2007) Morphological analysis of tumor cell/endothelial cell interactions under shear flow. J Biomech 40:335–344
Cinamon G, Alon R (2003) A real time in vitro assay for studying leukocyte transendothelial migration under physiological flow conditions. J Immunol Methods 273:53–62
Clark AM, Wheeler SE, Young CL, Stockdale L, Shepard Neiman J, Zhao W, Stolz DB, Venkataramanan R, Lauffenburger D, Griffith L, Wells A (2016) A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties. Lab Chip 17(1):156–168
Cooke JP, Stamler J, Andon N, Davies PF, McKinley G (1990) Flow stimulates endothelial cells to release a nitrovasodilator that is potentiated by reduced thiol. Am J Phys 259:H804–H812
van den Berg BM, Vink H, Spaan JA (2003) The endothelial glycocalyx protects against myocardial edema. Circ Res 92:592–594
Dereli-Korkut Z, Akaydin D, Ahmed AHR, Jiang X, Wang S (2014) Three dimensional microfluidic cell arrays for ex vivo drug screening with mimicked vascular flow. Anal Chem 86(6):2997–3004
Drenckhahn D, Ness W (1997) The endothelial contractile cytoskeleton. In: Born GVR, Schwartz CJ (eds) Vascular endothelium: physiology, pathology and therapeutic opportunities. Schattauer, Stuttgart, Gennany, pp 1–15
Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039
Earley S, Plopper GE (2006) Disruption of focal adhesion kinase slows transendothelial migration of AU-565 breast cancer cells. Biochem Biophys Res Commun 350:405–412
Ebong EE, Macaluso FP, Spray DC, Tarbell JM (2011) Imaging the endothelial glycocalyx in vitro by rapid freezing/freeze substitution transmission electron microscopy. Arterioscler Thromb Vasc Biol 31(8): 1908–1915
Fan J, Fu BM (2016) Quantification of malignant breast cancer cell MDA-MB-231 transmigration across brain and lung microvascular endothelium. Annals of Biomed Eng 44(7):2189–2201
Fan J, Cai B, Zeng M, Hao Y, Giancotti FG, Fu BM (2011) Integrin β4 signaling promotes mammary tumor cell adhesion to brain microvascular endothelium by inducing ErbB2-medicated secretion of VEGF. Ann of Biomed Eng 39(8):2223–2241
Feng D, Nagy JA, Payne K, Hammel I, Dvorak HF, Dvorak AM (1999) Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators. Microcirculation 6(1):23–44
Ferreira MM, Ramani VC, Jeffrey SS (2016) Circulating tumor cell technologies. Mol Oncol 10(3):374–394
Fidler IJ (2011) The biology of cancer metastasis. Semin Cancer Biol 21:71
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186
Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829–837
Fu BM, Shen S (2003) Structural mechanisms of vascular endothelial growth factor (VEGF) on microvessel permeability. Am J Phys 284(6):H2124–H2135
Fu BM, Shen S (2004) Acute VEGF effect on solution permeability of mammalian microvessels in vivo. Microvasc Res 68(1):51–62
Fu BM, Tarbell JM (2013) Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function. Wiley Interdiscip Rev Syst Biol Med 5:381–390
Fu BM, Weinbaum S, Tsay RY, Curry FE (1994) A junction-orifice-fiber entrance layer model for capillary permeability: application to frog mesenteric capillaries. ASME J Biomech Eng 116:502–513
Fu BM, Chen B, Chen W (2003) An electrodiffusion model for effects of surface glycocalyx layer on microvessel solute permeability. Am J Phys 284: H1240–H1250
Fu BM, Shen S, Chen B (2006) Structural mechanisms in the abolishment of VEGF-induced microvascular hyperpermeability by cAMP. ASME J. Biomech. Eng. 128(3):313–328
Fu BM, Yang J, Shen S, Cai B, Fan J, Zhang L, Yen WY, Zeng M (2015) Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo. Scientific Reports Oct 28
Gassmann P, Kang ML, Mees ST, Haier J (2010) In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell-endothelial cell interaction. BMC Cancer 10(177)
Giancotti FG (2007) Targeting integrin beta4 for cancer and anti-angiogenic therapy. Trends Pharmacol Sci 28:506–511
Giavazzi R, Foppolo M, Dossi R, Remuzzi A (1993) Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions. J Clin Invest 92:3038–3044
Glinskii OV, Huxley VH, Glinsky GV, Pienta KJ, Raz A, Glinsky VV (2005) Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs. Neoplasia 7(5):522–527
Guck J, Schinkinger S, Lincoln B, Wottawah F, Ebert S, Romeyke M, Lenz D, Erickson HM, Ananthakrishnan R, Mitchell D, Kas J, Ulvick S, Bilby C (2005) Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys J 88(5):3689–3698
Guo W, Giancotti FG (2004) Integrin signalling during tumour progression. Nat Rev Mol Cell Biol 5:816–826
Guo W, Pylayeva Y, Pepe A, Yoshioka T, Muller WJ, Inghirami G, Giancotti FG (2006) Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 126:489–502
Guo P, Cai B, Lei M, Liu Y, Fu BM (2014) Differential arrest and adhesion of tumor cells and microbeads in the microvasculature. Biomech Model Mechanobiol 13:537–550
Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127:679–695
van Hinsbergh VW, Nieuw Amerongen GP (2002) Intracellular signalling involved in modulating human endothelial barrier function. J Anat 200:549–560
Hood JD, Cheresh DA (2002) Role of integrins in cell invasion and migration. Nat Rev Cancer 2:91–100
Jeon JS, Bersini S, Gilardi M, Dubini G, Charest JL, Moretti M, Kamm RD (2015) Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation. Proc Natl Acad Sci U S A 112(1):214–219
Jiang X, Wong KHK, Khankhel AH, Zeinali M, Reategui E, Phillips MJ, Luo X, Aceto N, Fachin F, Hoang AN, Kim W, Jensen AE, Sequist LV, Maheswaran S, Haber DA, Stott SL, Toner M (2017) Microfluidic isolation of platelet-covered circulating tumor cells. Lab Chip 17(20):3498–3503
Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549
Khamenehfar A, Li PC (2016) Microfluidic devices for circulating tumor cells isolation and subsequent analysis. Curr Pharm Biotechnol 17(9):810–821
Khoo BL, Grenci G, Lim YB, Lee SC, Han J, Lim CT (2018) Expansion of patient-derived circulating tumor cells from liquid biopsies using a CTC microfluidic culture device. Nat Protoc 13(1):34–58
Kielbik M, Szulc I, Brzezinska M, Bednarska K, Przygodzka P (2014) Nitric oxide donors reduce the invasion ability of ovarian cancer cells in vitro. Anti-Cancer Drugs 25:1141–1151
Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WE, Goldbrunner R, Herms J, Winkle F (2010) Real-time imaging reveals the single steps of brain metastasis formation. Nature Med 16(1):116–122
Kong L, Dunn GD, Keefer LK, Korthuis RJ (1996) Nitric oxide reduces tumor cell adhesion to isolated rat postcapillary venules. Clin Exp Metastasis 14: 335–343
Kong J, Luo Y, Jin D, An F, Zhang W, Liu L, Li J, Fang S, Li X, Yang X, Lin B, Liu T (2016) A novel microfluidic model can mimic organ-specific metastasis of circulating tumor cells. Oncotarget 7(48):78421–78432
Koop S, MacDonald IC, Luzzi K, Schmidt EE, Morris VL, Grattan M, Khokha R, Chambers AF, Groom AC (1995) Fate of melanoma cells entering the microcirculation: over 80% survive and extravasate. Cancer Res 55(12):2520–2523
Lauffenburger DA, Horwitz AF (1996) Cell migration: a physically integrated molecular process. Cell 84: 359–369
Lee TH, Avraham HK, Jiang S, Avraham S (2003) Vascular endothelial growth factor modulates the transendothelial migration of MDA-MB-231 breast cancer cells through regulation of brain microvascular endothelial cell permeability. J Biol Chem 278: 5277–5284
Li LM, Kilbourn RG, Adams J, Fidler IJ (1991) Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells. Cancer Res 51:2531–2535
Li QS, Lee GY, Ong CN, Lim CT (2008) AFM indentation study of breast cancer cells. Biochem Biophys Res Commun 374(4):13–609
Li G, Simon M, Shi Z, Cancel L, Tarbell JM, Morrison B, Fu BM (2010) Permeability of endothelial and astrocyte cocultures: in vitro blood-brain barrier models for drug delivery. Ann of Biomed Eng 38(8):2499–2511
Liang S, Slattery MJ, Dong C (2005) Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion. Exp Cell Res 310(2):282–292
Litjens SH, de Pereda JM, Sonnenberg A (2006) Current insights into the formation and breakdown of hemidesmosomes. Trends Cell Biol 16:376–383
Liu Q, Mirc D, Fu BM (2008) Mechanical mechanisms of thrombosis in intact bent microvessels of rat mesentery. J Biomech 41:2726–2734
Liu Z, Han X, Zhou Q, Chen R, Fruge S, Jo MC, Ma Y, Li Z, Yokoi K, Qin L (2017) Integrated microfluidic system for gene silencing and cell migration. Adv Biosyst 1(6)
Lu Y, Yu T, Liang H, Wang J, Xie J (2014) Nitric oxide inhibits hetero-adhesion of cancer cells to endothelial cells: restraining circulating tumor cells from initiating metastatic cascade. Sci Rep 4:4344
Luft JH (1966) Fine structures of capillary and endocapillary layer as revealed by ruthenium red. Fed Proc 25(6):1773–1783
Masri FA, Comhair SA, Koeck T, Xu W, Janocha A (2005) Abnormalities in nitric oxide and its derivatives in lung cancer. Am J Respir Crit Care Med 172:597–605
Matsumoto K, Nishi K, Kikuchi M, Kadowaki D, Tokutomi Y (2007) Alpha1-acid glycoprotein suppresses rat acute inflammatory paw edema through the inhibition of neutrophils activation and prostaglandin E2 generation. Biol Pharm Bull 30:1226–1230
Michel CC, Curry FE (1999) Microvascular permeability. Physiol Reviews 79(3):703–761
Michel CC, Neal CR (1999) Openings through endothelial cells associated with increased microvascular permeability. Microcirculation 6(1):45–62
Mierke CT (2008) Role of the endothelium during tumor cell metastasis: is the endothelium a barrier or a promoter for cell invasion and metastasis. J Biophys 2008:183516
Minn AJ, Kang Y, Serganova I, Gupta GP, Giri DD et al (2005) Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest 115:44–55
Moasser MM, Basso A, Averbuch SD, Rosen N (2001) The tyrosine kinase inhibitor ZD1839 (“Iressa”) inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res 61:7184–7188
Mook ORF, Marle J, Vreeling-Sindelarova H, Jongens R, Frederiks WM, Noorden CJK (2003) Visualisation of early events in tumor formation of eGFP-transfected rat colon cancer cells in liver. Hepatology 38:295–304
Mortensen K, Christensen IJ, Nielsen HJ, Hansen U, Larsson LI (2004) High expression of endothelial cell nitric oxide synthase in peritumoral microvessels predicts increased disease-free survival in colorectal cancer. Cancer Lett 216:109–114
Mukhopadhyay D, Nagy JA, Manseau EJ, Dvorak HF (1998) Vascular permeability factor/vascular endothelial growth factor-mediated signaling in mouse mesentery vascular endothelium. Cancer Res 58(6): 1278–1284
Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284
Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L (2006) VEGF receptor signalling—in control of vascular function. Nat Rev Mol Cell Biol 7(5):359–371
Pohl U, Herlan K, Huang A, Bassenge E (1991) EDRF-mediated shear-induced dilation opposes myogenic vasoconstriction in small rabbit arteries. Am J Physiol 261:H2016–2023
Qiu H, Orr FW, Jensen D, Wang HH, McIntosh AR et al (2003) Arrest of B16 melanoma cells in the mouse pulmonary microcirculation induces endothelial nitric oxide synthase-dependent nitric oxide release that is cytotoxic to the tumor cells. Am J Pathol 162:403–412
Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflug Arch: Eur J Physiol 454:345–359
Ridnour LA, Thomas DD, Donzelli S, Espey MG, Roberts DD (2006) The biphasic nature of nitric oxide responses in tumor biology. Antioxid Redox Signal 8:1329–1337
Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial enestration induced by vascular endothelial growth factor. J Cell Sci 108:2369–2379
Salmon AH, Satchell SC (2012) Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J Pathol 226(4):562–574
Salmon AH, Neal CR, Sage LM, Glass CA, Harper SJ, Bates DO (2009) Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyx. Cardiovasc Res 83(1):24–33
Scher RL (2007) Role of nitric oxide in the development of distant metastasis from squamous cell carcinoma. Laryngoscope 117:199–209
Schluter K, Gassmann P, Enns A, Korb T, Hemping-Bovenkerk A, Holzen J, Haier J (2006) Organ-specific metastatic tumor cell adhesion and extravasation of colon carcinoma cells with different metastatic potential. Am J Pathol 169:1064–1073
Shea DJ, Li YW, Stebe KJ, Konstantopoulos K (2017) E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid. FASEB J 31(11):5078–5086
Shen S, Fan J, Cai B, Lv Y, Zeng M, Hao Y, Giancotti F, Fu BM (2010) Vascular endothelial growth factor enhances mammary cancer cell adhesion to endothelium in vivo. J of Exp Physiology 95:369–379
Shi L, Zeng M, Sun Y, Fu BM (2014) Quantification of blood-brain barrier solute permeability and brain transport by multiphoton microscopy. J Biomech Eng 136:031005
Slattery MJ, Liang S, Dong C (2005) Distinct role of hydrodynamic shear in leukocyte-facilitated tumor cell extravasation. Am J Phys 288:C831–C839
Squire JM, Chew M, Nneji G, Neal C, Barry J, Michel CC (2001) Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible explanation for molecular filtering? J Struct Biol 136:239–255
Steeg PS, Theodorescu D (2008) Metastasis: a therapeutic target for cancer. Nat Clin Pract Oncol 5(4):206–219
Steinbauer M, Guba M, Cernaianu G, Köhl G, Cetto M, Kunz-Schugart LA, Gcissler EK, Falk W, Jauch KW (2003) GFP-transfected tumor cells are useful in examining early metastasis in vivo, but immune reaction precludes long-term development studies in immunocompetent mice. Clin Exp Metastasis 20: 135–141
Strell C, Entschladen F (2008) Extravasation of leukocytes in comparison to tumor cells. Cell Commun Signal 6:10
Swaminathan V, Mythreye K, O’Brien ET, Berchuck A, Blobe GC, Superfine R (2011) Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Res 71(15):5075–5080
Tadimety A, Syed A, Nie Y, Long CR, Kready KM, Zhang JX (2017) Liquid biopsy on chip: a paradigm shift towards the understanding of cancer metastasis. Integr Biol (Camb) 23 9(1):22–49
Talmadge JE, Fidler IJ (2010) AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res 70:5649–5669
Tarbell JM, Pahakis MY (2006) Mechanotransduction and the glycocalyx. J Intern Med 259:339–350
Tobler NE, Detmar M (2006) Tumor and lymph node lymphangiogenesis--impact on cancer metastasis. J Leukoc Biol 80:691–696
Um E, Oh JM, Granick S, Cho YK (2017) Cell migration in microengineered tumor environments. Lab Chip 17(24):4171–4185
Vink H, Duling BR (1996) Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. Circ Res 79:581–589
Wang HH, McIntosh AR, Hasinoff BB, Rector ES, Ahmed N et al (2000) B16 melanoma cell arrest in the mouse liver induces nitric oxide release and sinusoidal cytotoxicity: a natural hepatic defense against metastasis. Cancer Res 60:5862–5869
Weber GF (2007) Molecular mechanisms of cancer. Springer, Netherlands
Weiss L (1992) Comments on hematogenous metastatic patterns in humans as revealed by autopsy. Clin Exp Metastasis 10:191–199
Wirtz DKK, Searson PC (2012) The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer 11:512
Wyckoff JB, Jones JG, Condeelis JS, Segall JE (2000) A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res 60:2504–2511
Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG (2002) The role of nitric oxide in cancer. Cell Res 12:311–320
Yan WW, Liu Y, Fu BM (2010) Effects of curvature and cell-cell interaction on cell adhesion in microvessels. Biomech Model Mechanobiol 9:629–640
Yan WW, Cai B, Liu Y, Fu BM (2012) Effects of wall shear stress and its gradient on tumor cell adhesion in curved microvessels. Biomech Model Mechanobiol 11(5):641–653. https://doi.org/10.1007/s10237-011-0339-6
Yen WY, Cai B, Zeng M, Tarbell JM, Fu BM (2012) Quantification of the endothelial surface glycocalyx on rat and mouse blood vessels. Microvasc Res
Yen WY, Cai B, Yang J, Zhang L, Zeng M, Tarbell JM, Fu BM (2015) Endothelial surface glycocalyx can regulate flow-induced endothelial NO production in microvessels in vivo. PLoS One 10(1):e0117133
Yudoh K, Matsui H, Tsuji H (1997) Nitric oxide induced by tumor cells activates tumor cell adhesion to endothelial cells and permeability of the endothelium in vitro. Clin Exp Metastasis 15:557–567
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(34):13515–13520
Zhang L, Zeng M, Fu BM (2016a) Inhibition of endothelial nitric oxide synthase decreases breast cancer cell MDA-MB-231 adhesion to intact microvessels under physiological flows. Am J Physiol Heart Circ Physiol 310(11):H1735–H1747
Zhang L, Fan J, Zeng M, Curry F-RE, John MT, Fu BM (2016b) Sphingosine-1-phosphate (S1P) maintains normal microvascular permeability by preserving endothelial surface glycocalyx (ESG) in intact microvessels. Microcirculation 23(4):301–310
Zhang L, Zeng M, Fu BM (2017) Sphingosine-1-phosphate reduces adhesion of malignant mammary tumor cells MDA-MB-231 to microvessel walls by protecting endothelialsurface glycocalyx. Cell Mol Biol (Noisy-le-Grand) 63(4):16–22
Acknowledgments
This work was supported by the NSF CBET 0754158, NIH CA153325-01, CA137788-01, and 1UG3TR002151-01.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Fu, B.M. (2018). Tumor Metastasis in the Microcirculation. In: Fu, B., Wright, N. (eds) Molecular, Cellular, and Tissue Engineering of the Vascular System. Advances in Experimental Medicine and Biology, vol 1097. Springer, Cham. https://doi.org/10.1007/978-3-319-96445-4_11
Download citation
DOI: https://doi.org/10.1007/978-3-319-96445-4_11
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-96444-7
Online ISBN: 978-3-319-96445-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)