, Volume 16, Issue 4, pp 847–860 | Cite as

Prostate specific membrane antigen produces pro-angiogenic laminin peptides downstream of matrix metalloprotease-2

  • Rebecca E. ConwayEmail author
  • Kyle Joiner
  • Alex Patterson
  • David Bourgeois
  • Robert Rampp
  • Benjamin C. Hannah
  • Samantha McReynolds
  • John M. Elder
  • Hannah Gilfilen
  • Linda H. Shapiro
Original Paper


Prostate specific membrane antigen (PSMA) is a pro-angiogenic cell-surface protease that we previously demonstrated regulates blood vessel formation in a laminin and integrin β1-dependent manner. Here, we examine the principal mechanism of PSMA activation of integrin β1. We show that digesting laminin sequentially with recombinant matrix metalloprotease-2 (MMP-2) and PSMA generates small peptides that enhance endothelial cell adhesion and migration in vitro. We also provide evidence that these laminin peptides activate adhesion via integrin α6β1 and focal adhesion kinase. Using an in vivo Matrigel implant assay, we show that these MMP/PSMA-derived laminin peptides also increase angiogenesis in vivo. Together, our results reveal a novel mechanism of PSMA activation of angiogenesis by processing laminin downstream of MMP-2.


Angiogenesis Extracellular matrix Prostate specific membrane antigen Matrix metalloproteases 



The authors wish to acknowledge Amanda Williams for her technical support, Drs. Kent Gallaher Jon Lowrance, and Kent Clinger for their advice and support, Dylan Addis, Brian Burress, and Ryan Hudson for their preliminary research leading to this work, Joe Angevine for his technical assistance, and the Langford Yates Fellowship for partial financial support of this study. This work was supported, in part, by the Prostate Cancer Foundation and the Department of Defense Grant PC073976.

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Sprenger CC, Plymate SR, Reed MJ (2010) Aging-related alterations in the extracellular matrix modulate the microenvironment and influence tumor progression. Int J Cancer J Int du Cancer 127(12):2739–2748. doi: 10.1002/ijc.25615 CrossRefGoogle Scholar
  2. 2.
    Schedin P, Keely PJ (2011) Mammary gland ECM remodeling, stiffness, and mechanosignaling in normal development and tumor progression. Cold Spring Harb Perspect Biol 3(1):a003228. doi: 10.1101/cshperspect.a003228 PubMedCrossRefGoogle Scholar
  3. 3.
    Bremnes RM, Donnem T, Al-Saad S, Al-Shibli K, Andersen S, Sirera R, Camps C, Marinez I, Busund LT (2011) The role of tumor stroma in cancer progression and prognosis: emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer. J Thorac Oncol 6(1):209–217. doi: 10.1097/JTO.0b013e3181f8a1bd PubMedCrossRefGoogle Scholar
  4. 4.
    Schulz WA, Ingenwerth M, Djuidje CE, Hader C, Rahnenfuhrer J, Engers R (2010) Changes in cortical cytoskeletal and extracellular matrix gene expression in prostate cancer are related to oncogenic ERG deregulation. BMC cancer 10:505. doi: 10.1186/1471-2407-10-505 PubMedCrossRefGoogle Scholar
  5. 5.
    Humphries MJ, Olden K, Yamada KM (1986) A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 233(4762):467–470PubMedCrossRefGoogle Scholar
  6. 6.
    Ponce ML, Hibino S, Lebioda AM, Mochizuki M, Nomizu M, Kleinman HK (2003) Identification of a potent peptide antagonist to an active laminin-1 sequence that blocks angiogenesis and tumor growth. Cancer Res 63(16):5060–5064PubMedGoogle Scholar
  7. 7.
    Yamada T, Tsuda M, Takahashi T, Totsuka Y, Shindoh M, Ohba Y (2011) RANKL expression specifically observed in vivo promotes epithelial mesenchymal transition and tumor progression. Am J Pathol 178(6):2845–2856. doi: 10.1016/j.ajpath.2011.02.003 PubMedCrossRefGoogle Scholar
  8. 8.
    Maeshima Y, Colorado PC, Torre A, Holthaus KA, Grunkemeyer JA, Ericksen MB, Hopfer H, Xiao Y, Stillman IE, Kalluri R (2000) Distinct antitumor properties of a type IV collagen domain derived from basement membrane. J Biol Chem 275(28):21340–21348. doi: 10.1074/jbc.M001956200 PubMedCrossRefGoogle Scholar
  9. 9.
    O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88(2):277–285PubMedCrossRefGoogle Scholar
  10. 10.
    O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Cao Y, Moses M, Lane WS, Sage EH, Folkman J (1994) Angiostatin: a circulating endothelial cell inhibitor that suppresses angiogenesis and tumor growth. Cold Spring Harb Symp Quant Biol 59:471–482PubMedCrossRefGoogle Scholar
  11. 11.
    Maeshima Y, Sudhakar A, Lively JC, Ueki K, Kharbanda S, Kahn CR, Sonenberg N, Hynes RO, Kalluri R (2002) Tumstatin, an endothelial cell-specific inhibitor of protein synthesis. Science 295(5552):140–143. doi: 10.1126/science.1065298 PubMedCrossRefGoogle Scholar
  12. 12.
    Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, Torre A, Maeshima Y, Mier JW, Sukhatme VP, Kalluri R (2000) Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem 275(2):1209–1215PubMedCrossRefGoogle Scholar
  13. 13.
    Felbor U, Mutsch Y, Grehn F, Muller CR, Kress W (1999) Ocular ochronosis in alkaptonuria patients carrying mutations in the homogentisate 1,2-dioxygenase gene. Br J Ophthalmol 83(6):680–683PubMedCrossRefGoogle Scholar
  14. 14.
    Xu J, Kim GM, Ahmed SH, Xu J, Yan P, Xu XM, Hsu CY (2001) Glucocorticoid receptor-mediated suppression of activator protein-1 activation and matrix metalloproteinase expression after spinal cord injury. J Neurosci Off J Soc Neurosci 21(1):92–97Google Scholar
  15. 15.
    Koshikawa N, Giannelli G, Cirulli V, Miyazaki K, Quaranta V (2000) Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5. J Cell Biol 148(3):615–624PubMedCrossRefGoogle Scholar
  16. 16.
    Risau W, Lemmon V (1988) Changes in the vascular extracellular matrix during embryonic vasculogenesis and angiogenesis. Dev Biol 125(2):441–450PubMedCrossRefGoogle Scholar
  17. 17.
    Ljubimova JY, Fujita M, Khazenzon NM, Ljubimov AV, Black KL (2006) Changes in laminin isoforms associated with brain tumor invasion and angiogenesis. Front Biosci 11:81–88PubMedCrossRefGoogle Scholar
  18. 18.
    Kibbey MC, Grant DS, Kleinman HK (1992) Role of the SIKVAV site of laminin in promotion of angiogenesis and tumor growth: an in vivo Matrigel model. J Natl Cancer Inst 84(21):1633–1638PubMedCrossRefGoogle Scholar
  19. 19.
    Malinda KM, Nomizu M, Chung M, Delgado M, Kuratomi Y, Yamada Y, Kleinman HK, Ponce ML (1999) Identification of laminin α1 and β1 chain peptides active for endothelial cell adhesion, tube formation, and aortic sprouting. FASEB J 13(1):53–62PubMedGoogle Scholar
  20. 20.
    Mochizuki M, Philp D, Hozumi K, Suzuki N, Yamada Y, Kleinman HK, Nomizu M (2007) Angiogenic activity of syndecan-binding laminin peptide AG73 (RKRLQVQLSIRT). Arch Biochem Biophys 459(2):249–255. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  21. 21.
    Nomizu M, Weeks BS, Weston CA, Kim WH, Kleinman HK, Yamada Y (1995) Structure-activity study of a laminin α1 chain active peptide segment Ile-Lys-Val-Ala-Val (IKVAV). FEBS Lett 365(2–3):227–231PubMedCrossRefGoogle Scholar
  22. 22.
    Aumailley M, Timpl R, Risau W (1991) Differences in laminin fragment interactions of normal and transformed endothelial cells. Exp Cell Res 196(2):177–183PubMedCrossRefGoogle Scholar
  23. 23.
    Wu ZS, Wu Q, Yang JH, Wang HQ, Ding XD, Yang F, Xu XC (2008) Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int J Cancer J Int du Cancer 122(9):2050–2056. doi: 10.1002/ijc.23337 CrossRefGoogle Scholar
  24. 24.
    La Rocca G, Pucci-Minafra I, Marrazzo A, Taormina P, Minafra S (2004) Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera. Br J Cancer 90(7):1414–1421. doi: 10.1038/sj.bjc.6601725 PubMedCrossRefGoogle Scholar
  25. 25.
    Poola I, DeWitty RL, Marshalleck JJ, Bhatnagar R, Abraham J, Leffall LD (2005) Identification of MMP-1 as a putative breast cancer predictive marker by global gene expression analysis. Nat Med 11(5):481–483. doi: 10.1038/nm1243 PubMedCrossRefGoogle Scholar
  26. 26.
    Koc M, Ediger D, Budak F, Karadag M, Oral HB, Uzaslan E, Ege E, Gozu RO (2006) Matrix metalloproteinase-9 (MMP-9) elevated in serum but not in bronchial lavage fluid in patients with lung cancer. Tumori 92(2):149–154PubMedGoogle Scholar
  27. 27.
    Morgia G, Falsaperla M, Malaponte G, Madonia M, Indelicato M, Travali S, Mazzarino MC (2005) Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer. Urol Res 33(1):44–50. doi: 10.1007/s00240-004-0440-8 PubMedCrossRefGoogle Scholar
  28. 28.
    Montesano R, Mouron P, Orci L (1985) Vascular outgrowths from tissue explants embedded in fibrin or collagen gels: a simple in vitro model of angiogenesis. Cell Biol Int Rep 9(10):869–875PubMedCrossRefGoogle Scholar
  29. 29.
    Mabeta P, Pepper MS (2009) A comparative study on the anti-angiogenic effects of DNA-damaging and cytoskeletal-disrupting agents. Angiogenesis 12(1):81–90. doi: 10.1007/s10456-009-9134-8 PubMedCrossRefGoogle Scholar
  30. 30.
    Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I (1988) A heparin-binding angiogenic protein-basic fibroblast growth factor is stored within basement membrane. Am J Pathol 130(2):393–400PubMedGoogle Scholar
  31. 31.
    O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79(2):315–328PubMedCrossRefGoogle Scholar
  32. 32.
    Lane TF, Iruela-Arispe ML, Johnson RS, Sage EH (1994) SPARC is a source of copper-binding peptides that stimulate angiogenesis. J Cell Biol 125(4):929–943PubMedCrossRefGoogle Scholar
  33. 33.
    Wang J, Milner R (2006) Fibronectin promotes brain capillary endothelial cell survival and proliferation through α5β1 and αvβ3 integrins via MAP kinase signalling. J Neurochem 96(1):148–159. doi: 10.1111/j.1471-4159.2005.03521.x PubMedCrossRefGoogle Scholar
  34. 34.
    McDaniel SM, Rumer KK, Biroc SL, Metz RP, Singh M, Porter W, Schedin P (2006) Remodeling of the mammary microenvironment after lactation promotes breast tumor cell metastasis. Am J Pathology 168(2):608–620. doi: 10.2353/ajpath.2006.050677 CrossRefGoogle Scholar
  35. 35.
    Roy M, Marchetti D (2009) Cell surface heparan sulfate released by heparanase promotes melanoma cell migration and angiogenesis. J Cell Biochem 106(2):200–209. doi: 10.1002/jcb.22005 PubMedCrossRefGoogle Scholar
  36. 36.
    Bhagwat SV, Lahdenranta J, Giordano R, Arap W, Pasqualini R, Shapiro LH (2001) CD13/APN is activated by angiogenic signals and is essential for capillary tube formation. Blood 97(3):652–659PubMedCrossRefGoogle Scholar
  37. 37.
    Chen J, Zhang ZG, Li Y, Wang Y, Wang L, Jiang H, Zhang C, Lu M, Katakowski M, Feldkamp CS, Chopp M (2003) Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann Neurol 53(6):743–751. doi: 10.1002/ana.10555 PubMedCrossRefGoogle Scholar
  38. 38.
    Marchio S, Lahdenranta J, Schlingemann RO, Valdembri D, Wesseling P, Arap MA, Hajitou A, Ozawa MG, Trepel M, Giordano RJ, Nanus DM, Dijkman HB, Oosterwijk E, Sidman RL, Cooper MD, Bussolino F, Pasqualini R, Arap W (2004) Aminopeptidase A is a functional target in angiogenic blood vessels. Cancer Cell 5(2):151–162PubMedCrossRefGoogle Scholar
  39. 39.
    Conway RE, Petrovic N, Li Z, Heston W, Wu D, Shapiro LH (2006) Prostate-specific membrane antigen regulates angiogenesis by modulating integrin signal transduction. Mol Cell Biol 26(14):5310–5324. doi: 10.1128/MCB.00084-06 PubMedCrossRefGoogle Scholar
  40. 40.
    Horoszewicz JS, Kawinski E, Murphy GP (1987) Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res 7(5B):927–935PubMedGoogle Scholar
  41. 41.
    Israeli RS, Powell CT, Fair WR, Heston WD (1993) Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res 53(2):227–230PubMedGoogle Scholar
  42. 42.
    Israeli RS, Miller WH Jr, Su SL, Samadi DS, Powell CT, Heston WD, Wise GJ, Fair WR (1995) Sensitive detection of prostatic hematogenous tumor cell dissemination using prostate specific antigen and prostate specific membrane-derived primers in the polymerase chain reaction. J Urol 153(3 Pt 1):573–577PubMedGoogle Scholar
  43. 43.
    Drachenberg DE, Elgamal AA, Rowbotham R, Peterson M, Murphy GP (1999) Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer. Prostate 41(2):127–133PubMedCrossRefGoogle Scholar
  44. 44.
    Liu H, Moy P, Kim S, Xia Y, Rajasekaran A, Navarro V, Knudsen B, Bander NH (1997) Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 57(17):3629–3634PubMedGoogle Scholar
  45. 45.
    Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res Off J Am Assoc Cancer Res 3(1):81–85Google Scholar
  46. 46.
    Chang SS, Heston WD (2002) The clinical role of prostate-specific membrane antigen (PSMA). Urol Oncol 7(1):7–12PubMedCrossRefGoogle Scholar
  47. 47.
    Carter RE, Feldman AR, Coyle JT (1996) Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc Natl Acad Sci USA 93(2):749–753PubMedCrossRefGoogle Scholar
  48. 48.
    Tiffany CW, Lapidus RG, Merion A, Calvin DC, Slusher BS (1999) Characterization of the enzymatic activity of PSM: comparison with brain NAALADase. Prostate 39(1):28–35PubMedCrossRefGoogle Scholar
  49. 49.
    Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, May F, Mukherjee B, Heston WD (1996) Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res Off J Am Assoc Cancer Res 2(9):1445–1451Google Scholar
  50. 50.
    Chia J, Kusuma N, Anderson R, Parker B, Bidwell B, Zamurs L, Nice E, Pouliot N (2007) Evidence for a role of tumor-derived laminin-511 in the metastatic progression of breast cancer. Am J Pathol 170(6):2135–2148. doi: 10.2353/ajpath.2007.060709 PubMedCrossRefGoogle Scholar
  51. 51.
    Fujita M, Khazenzon NM, Bose S, Sekiguchi K, Sasaki T, Carter WG, Ljubimov AV, Black KL, Ljubimova JY (2005) Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases. Breast Cancer Res BCR 7(4):R411–R421. doi: 10.1186/bcr1011 CrossRefGoogle Scholar
  52. 52.
    Miner JH, Yurchenco PD (2004) Laminin functions in tissue morphogenesis. Ann Rev Cell Dev Biol 20:255–284. doi: 10.1146/annurev.cellbio.20.010403.094555 CrossRefGoogle Scholar
  53. 53.
    Mesters JR, Barinka C, Li W, Tsukamoto T, Majer P, Slusher BS, Konvalinka J, Hilgenfeld R (2006) Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer. EMBO J 25(6):1375–1384. doi: 10.1038/sj.emboj.7600969 PubMedCrossRefGoogle Scholar
  54. 54.
    Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141(1):52–67. doi: 10.1016/j.cell.2010.03.015 PubMedCrossRefGoogle Scholar
  55. 55.
    Mydel P, Shipley JM, Adair-Kirk TL, Kelley DG, Broekelmann TJ, Mecham RP, Senior RM (2008) Neutrophil elastase cleaves laminin-332 (laminin-5) generating peptides that are chemotactic for neutrophils. J Biol Chem 283(15):9513–9522. doi: 10.1074/jbc.M706239200 PubMedCrossRefGoogle Scholar
  56. 56.
    Udayakumar TS, Chen ML, Bair EL, Von Bredow DC, Cress AE, Nagle RB, Bowden GT (2003) Membrane type-1-matrix metalloproteinase expressed by prostate carcinoma cells cleaves human laminin-5 β3 chain and induces cell migration. Cancer Res 63(9):2292–2299PubMedGoogle Scholar
  57. 57.
    Ohuchi E, Imai K, Fujii Y, Sato H, Seiki M, Okada Y (1997) Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem 272(4):2446–2451PubMedCrossRefGoogle Scholar
  58. 58.
    Littlepage LE, Sternlicht MD, Rougier N, Phillips J, Gallo E, Yu Y, Williams K, Brenot A, Gordon JI, Werb Z (2010) Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer Res 70(6):2224–2234. doi: 10.1158/0008-5472.CAN-09-3515 PubMedCrossRefGoogle Scholar
  59. 59.
    Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG, Quaranta V (1997) Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277(5323):225–228PubMedCrossRefGoogle Scholar
  60. 60.
    Giannelli G, Bergamini C, Fransvea E, Marinosci F, Quaranta V, Antonaci S (2001) Human hepatocellular carcinoma (HCC) cells require both α3β1 integrin and matrix metalloproteinases activity for migration and invasion. Lab Invest J Tech Methods Pathol 81(4):613–627CrossRefGoogle Scholar
  61. 61.
    Gu J, Nishiuchi R, Sekiguchi K (2002) Matrix metalloproteinase-2 is involved in A549 cell migration on laminin-10/11. Biochem Biophys Res Commun 296(1):73–77PubMedCrossRefGoogle Scholar
  62. 62.
    Heath TG, Giordani AB (1993) Reversed-phase capillary high-performance liquid chromatography with on-line UV, fluorescence and electrospray ionization mass spectrometric detection in the analysis of peptides and proteins. J Chromatogr 638(1):9–19PubMedCrossRefGoogle Scholar
  63. 63.
    Igarashi Y, Heureux E, Doctor KS, Talwar P, Gramatikova S, Gramatikoff K, Zhang Y, Blinov M, Ibragimova SS, Boyd S, Ratnikov B, Cieplak P, Godzik A, Smith JW, Osterman AL, Eroshkin AM (2009) PMAP: databases for analyzing proteolytic events and pathways. Nucleic Acids Res 37(Database issue):D611–D618. doi: 10.1093/nar/gkn683 PubMedCrossRefGoogle Scholar
  64. 64.
    Chen EI, Kridel SJ, Howard EW, Li W, Godzik A, Smith JW (2002) A unique substrate recognition profile for matrix metalloproteinase-2. J Biol Chem 277(6):4485–4491. doi: 10.1074/jbc.M109469200 PubMedCrossRefGoogle Scholar
  65. 65.
    Makino M, Okazaki I, Kasai S, Nishi N, Bougaeva M, Weeks BS, Otaka A, Nielsen PK, Yamada Y, Nomizu M (2002) Identification of cell binding sites in the laminin α5-chain G domain. Exp Cell Res 277(1):95–106. doi: 10.1006/excr.2002.5540 PubMedCrossRefGoogle Scholar
  66. 66.
    Baker AH, Wilkinson GW, Hembry RM, Murphy G, Newby AC (1996) Development of recombinant adenoviruses that drive high level expression of the human metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 and -2 genes: characterization of their infection into rabbit smooth muscle cells and human MCF-7 adenocarcinoma cells. Matrix Biol J Int Soc Matrix Biol 15(6):383–395CrossRefGoogle Scholar
  67. 67.
    Belkin AM, Stepp MA (2000) Integrins as receptors for laminins. Microsc Res Tech 51(3):280–301. doi: 10.1002/1097-0029(20001101)51:3<280:AID-JEMT7>3.0.CO;2-O PubMedCrossRefGoogle Scholar
  68. 68.
    Carter WG, Wayner EA, Bouchard TS, Kaur P (1990) The role of integrins α2β1 and α3β1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol 110(4):1387–1404PubMedCrossRefGoogle Scholar
  69. 69.
    Kramer RH (1994) Characterization of laminin-binding integrins. Methods Enzymol 245:129–147PubMedCrossRefGoogle Scholar
  70. 70.
    Lee TH, Seng S, Li H, Kennel SJ, Avraham HK, Avraham S (2006) Integrin regulation by vascular endothelial growth factor in human brain microvascular endothelial cells: role of α6β1 integrin in angiogenesis. J Biol Chem 281(52):40450–40460. doi: 10.1074/jbc.M607525200 PubMedCrossRefGoogle Scholar
  71. 71.
    Witkowski CM, Rabinovitz I, Nagle RB, Affinito KS, Cress AE (1993) Characterization of integrin subunits, cellular adhesion and tumorgenicity of four human prostate cell lines. J Cancer Res Clin Oncol 119(11):637–644PubMedCrossRefGoogle Scholar
  72. 72.
    da Silva RG, Tavora B, Robinson SD, Reynolds LE, Szekeres C, Lamar J, Batista S, Kostourou V, Germain MA, Reynolds AR, Jones DT, Watson AR, Jones JL, Harris A, Hart IR, Iruela-Arispe ML, Dipersio CM, Kreidberg JA, Hodivala-Dilke KM (2010) Endothelial α3β1-integrin represses pathological angiogenesis and sustains endothelial-VEGF. Am J Pathol 177(3):1534–1548. doi: 10.2353/ajpath.2010.100043 PubMedCrossRefGoogle Scholar
  73. 73.
    Ido H, Harada K, Futaki S, Hayashi Y, Nishiuchi R, Natsuka Y, Li S, Wada Y, Combs AC, Ervasti JM, Sekiguchi K (2004) Molecular dissection of the alpha-dystroglycan- and integrin-binding sites within the globular domain of human laminin-10. J Biol Chem 279(12):10946–10954. doi: 10.1074/jbc.M313626200 PubMedCrossRefGoogle Scholar
  74. 74.
    Kunneken K, Pohlentz G, Schmidt-Hederich A, Odenthal U, Smyth N, Peter-Katalinic J, Bruckner P, Eble JA (2004) Recombinant human laminin-5 domains. Effects of heterotrimerization, proteolytic processing, and N-glycosylation on α3β1 integrin binding. J Biol Chem 279(7):5184–5193. doi: 10.1074/jbc.M310424200 PubMedCrossRefGoogle Scholar
  75. 75.
    Ido H, Nakamura A, Kobayashi R, Ito S, Li S, Futaki S, Sekiguchi K (2007) The requirement of the glutamic acid residue at the third position from the carboxyl termini of the laminin gamma chains in integrin binding by laminins. J Biol Chem 282(15):11144–11154. doi: 10.1074/jbc.M609402200 PubMedCrossRefGoogle Scholar
  76. 76.
    Taniguchi Y, Ido H, Sanzen N, Hayashi M, Sato-Nishiuchi R, Futaki S, Sekiguchi K (2009) The C-terminal region of laminin beta chains modulates the integrin binding affinities of laminins. J Biol Chem 284(12):7820–7831. doi: 10.1074/jbc.M809332200 PubMedCrossRefGoogle Scholar
  77. 77.
    Vorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC (2000) Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2. J Immunol 165(4):2093–2100PubMedGoogle Scholar
  78. 78.
    Wickstrom SA, Alitalo K, Keski-Oja J (2004) An endostatin-derived peptide interacts with integrins and regulates actin cytoskeleton and migration of endothelial cells. J Biol Chem 279(19):20178–20185. doi: 10.1074/jbc.M312921200 PubMedCrossRefGoogle Scholar
  79. 79.
    Lishko VK, Podolnikova NP, Yakubenko VP, Yakovlev S, Medved L, Yadav SP, Ugarova TP (2004) Multiple binding sites in fibrinogen for integrin αMβ2 (Mac-1). J Biol Chem 279(43):44897–44906. doi: 10.1074/jbc.M408012200 PubMedCrossRefGoogle Scholar
  80. 80.
    Emsley J, Knight CG, Farndale RW, Barnes MJ, Liddington RC (2000) Structural basis of collagen recognition by integrin α2β1. Cell 101(1):47–56. doi: 10.1016/S0092-8674(00)80622-4 PubMedCrossRefGoogle Scholar
  81. 81.
    Shimaoka T, Nakayama T, Fukumoto N, Kume N, Takahashi S, Yamaguchi J, Minami M, Hayashida K, Kita T, Ohsumi J, Yoshie O, Yonehara S (2004) Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J Leukoc Biol 75(2):267–274. doi: 10.1189/jlb.1003465 PubMedCrossRefGoogle Scholar
  82. 82.
    Weathington NM, van Houwelingen AH, Noerager BD, Jackson PL, Kraneveld AD, Galin FS, Folkerts G, Nijkamp FP, Blalock JE (2006) A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med 12(3):317–323. doi: 10.1038/nm1361 PubMedCrossRefGoogle Scholar
  83. 83.
    Gaggar A, Jackson PL, Noerager BD, O’Reilly PJ, McQuaid DB, Rowe SM, Clancy JP, Blalock JE (2008) A novel proteolytic cascade generates an extracellular matrix-derived chemoattractant in chronic neutrophilic inflammation. J Immunol 180(8):5662–5669PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Rebecca E. Conway
    • 1
    • 2
    Email author
  • Kyle Joiner
    • 1
  • Alex Patterson
    • 1
  • David Bourgeois
    • 1
  • Robert Rampp
    • 1
  • Benjamin C. Hannah
    • 1
  • Samantha McReynolds
    • 1
  • John M. Elder
    • 1
  • Hannah Gilfilen
    • 1
  • Linda H. Shapiro
    • 2
  1. 1.Department of Biology, College of Arts and SciencesLipscomb UniversityNashvilleUSA
  2. 2.Department of Cell Biology, Center for Vascular BiologyUniversity of Connecticut Health CenterFarmingtonUSA

Personalised recommendations