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Basement membrane and the SIKVAV laminin-derived peptide promote tumor growth and metastases

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Summary

Laminin, the major glycoprotein component of basement membrane, promotes the malignant phenotype. Cells which are adherent to laminin are more malignant than the non-adherent cells and in certain tumor cells, the number of laminin receptors is positively correlated with malignancy. Laminin also increases collagenase IV activity, an enzyme demonstrated to be critical for tumor spread. A site on laminin, containing the amino acid sequence SIKVAV, has been identified which when injected intravenously with B16F10 melanoma cells, causes an increase in the number of colonies on the surface of the lungs. This peptide does not affect tumor cell arrest in the vasculature or the immune system. It does promote angiogenesis in various in vitro and in vivo models, thereby facilitating tumor cell survival.

When a complex mixture of laminin-enriched basement membrane components (Matrigel) is coinjected with tumor cells subcutaneously, tumor incidence and growth increases. Various tumor cell lines and primary isolates, which previously could not form tumors in mice, can be induced to grow rapidly in the presence of Matrigel. Slowly growing tumors or arrested tumors can also be induced to grow more quickly with additional injections of Matrigel. When an SIKVAV-containing synthetic peptide is coinjected with B16F10 tumor cells and Matrigel subcutaneously in mice, larger tumors are formed than that observed with either Matrigel or cells alone. Such studies define the role of laminin in tumor growth and spread and generate new models for studying therapeutic agents. Of particular interest is the ability to grow primary isolates which generally do not grow in mice.

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References

  1. Liotta LA, Rao CN, Wewer U: Biochemical interactions of tumor cells with the basement membrane. Ann Rev Biochem 55: 1037–1057, 1986

    Google Scholar 

  2. Martin GR, Timpl R: Laminin and other basement membrane components. Ann Rev Cell Biol 3: 57–85, 1987

    Google Scholar 

  3. Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW, Martin GR: Basement membrane complexes with biological activities. Biochem 25: 312–318, 1986

    Google Scholar 

  4. Kleinman HK, Graf J, Iwamoto Y, Kitten GT, Ogle RC, Sasaki M, Yamada Y, Martin GR, Luckenbill-Edds L: Role of basement membranes in cell differentiation. N Y Acad Sci 513: 134–145, 1987

    Google Scholar 

  5. Timpl R: Structure and biological activity of basement membrane proteins. Eur J Biochem 180: 487–502, 1989

    Google Scholar 

  6. Vlodavsky I, Gospodarowicz D: Respective roles of laminin and fibronectin in adhesion of human carcinoma and sarcoma cells. Nature (London) 289: 304–306, 1981

    Google Scholar 

  7. Rao CN, Margulies MK, Tralka TS, Terranova VP, Madri JA, Liotta LA: Isolation of a subunit of laminin and its role in molecular structure and tumor cell attachment. J Biol Chem 257: 974–979, 1982

    Google Scholar 

  8. Fridman R, Giaccone G, Kanemoto T, Martin GR, Gazdar AF, Mulshine JL: Reconstituted basement membrane (Matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer. Proc Natl Acad Sci USA 87: 6698–6702, 1990

    Google Scholar 

  9. Terranova VP, Liotta LA, Russo RG: Role of laminin in the attachment and metastasis of murine tumor cells. Cancer Res 42: 2265–2269, 1982

    Google Scholar 

  10. Terranova VP, Williams JE, Liotta LA, Martin GR: Modulation of the metastatic activity of melanoma cells by laminin and fibronectin. Sci 226: 982–985, 1984

    Google Scholar 

  11. Barsky SH, Rao CN, Williams JE, Liotta LA: Laminin molecular domains which alter metastasis in a murine model. J Clin Invest 74: 843–848, 1984

    Google Scholar 

  12. Wewer UM, Liotta LA, Jaye M, Ricca GA, Drohan WN, Claysmith AP, Rao CN, Wirth P, Coligan JE, Albrechtsen R, Mudryj M, Sobel M: Altered levels of laminin receptor mRNA in various human carcinoma cells that have different abilities to bind laminin. Proc Natl Acad Sci USA 83: 7137–7141, 1986

    Google Scholar 

  13. Yow H, Wong JM, Chen HS, Lee C, Steele GD, Chen LB: Increased mRNA expression of a laminin binding protein in human colon carcinoma. Complete sequence of a full-length cDNA encoding the protein. Proc Natl Acad Sci USA 85: 6394–6398, 1988

    Google Scholar 

  14. Turpeeniemi-Hujanen T, Thorgeisson UP, Rao CN, Liotta LA: Laminin increases the release of type IV collagenase. J Biol Chem 261: 1883–1889, 1986

    Google Scholar 

  15. Beck K, Hunter I, Engel J: Structure and function of laminin: anatomy of a multidomain glycoprotein. FASEB J 4: 148–160, 1990

    Google Scholar 

  16. Timpl R, Rohde H, Robey PG, Rennard SI, Foidart J, Martin GR: Laminin-a glycoprotein from basement membranes. J Biol Chem 254: 9933–9937, 1979

    Google Scholar 

  17. Kleinman HK, McGarvey ML, Liotta LA, Gehron Robey P, Tryggvason K, Martin GR: Isolation and characterization of native type IV collagen from the EHS sarcoma. Biochemistry 24: 6188–6193, 1982

    Google Scholar 

  18. Taub M, Wang Y, Szcesney TM, Kleinman HK, Martin GR: Transforming growth factor α is required for kidney tubulogenesis in Matrigel cultures in serum free medium. Proc Natl Acad Sci USA 87: 4002–4006, 1990

    Google Scholar 

  19. Vukicevic S, Kleinman HK, Luyten F, Roberts A, Reddi AH: Growth factors in reconstituted basement membrane (Matrigel) regulate network formation of MC 3T3-E1 Osteoblastic cells. Submitted

  20. Albini A, Iwamoto Y, Kleinman HK, Martin GR, Kozlowski JM, McEwan RN: A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 47: 3239–3245, 1987

    Google Scholar 

  21. Kramer RH, Bensch KG, Wong J: Invasion of reconstituted basement membrane matrix by metastatic human tumor cells. Cancer Res 46: 1980–1989, 1986

    Google Scholar 

  22. Terranova VP, Hujanen ES, Loeb DM, Martin GR, Thornburg L, Glushko V: Use of a reconstituted basement membrane to measure cell invasiveness and select for highly invasive tumor cells. Proc Natl Acad Sci USA 83: 465–469, 1989

    Google Scholar 

  23. Hendrix MJC, Seftor EA, Seftor REB, Misiorowski RL, Saba PZ, Sundareshan P, Welch DR: Comparison of tumor cell invasion assays: human amnion versus reconstituted basement membrane barriers. Invas and Metast 9: 278–297, 1989

    Google Scholar 

  24. Starkey JR: Cell-matrix interactions during tumor invasion. Cancer and Metast Rev 9: 113–123, 1990

    Google Scholar 

  25. Reich R, Thompson E, Iwamoto Y, Martin GR, Deason JR, Fuller GC, Miskin R: Effects of inhibitors of plasminogen activator, serine proteinases and collagenase IV on the invasion of basement membrane by metastatic cells. Cancer Res 48: 3307–3312, 1988

    Google Scholar 

  26. Wang M, Stearns ME: Blocking of collagenase secretion by estramustine during in vitro tumor invasion. Cancer Res 48: 6262–6271, 1988

    Google Scholar 

  27. Erkell LJ, Schirrmacker V: Quantitative in vitro assay for tumor cell invasion through extracellular matrix or into protein gels. Cancer Res 48: 6933–6937, 1988

    Google Scholar 

  28. Lester BR, McCarthy JB, Sun Z, Smith RS, Furcht LJ, Spiegel AM: G-protein involvement in matrix-mediated motility and invasion of high and low experimental metastatic B16 melanoma clones. Cancer Res 49: 5940–5948, 1989

    Google Scholar 

  29. Taniguchi S, Tasuka M, Nakamatsu K, Inoue M, Sadano H, Okazaki H, Iwamoto H, Baba T: High invasiveness associated with augmentation of motility in a fos-transferred highly metastatic rat 3Y1 cell line. Cancer Res 49: 6738–6744, 1989

    Google Scholar 

  30. McLemore TL, Liu MC, Blacker PC, Gregg M, Alley MC, Abbott BJ, Shoemaker RIL, Bohlman ME, Litterst CC, Hubbard WC, Brennan R, McMahon JB, Fine DL, Eggleston JC, Mayo JG, Boyd MR: Novel intrapulmonary model for orthotopic propagation of human cancers in athymic nude mice. Cancer Res 47: 5132–5140, 1982

    Google Scholar 

  31. Fridman R, Kibbey MC, Royce LS, Zain M, Sweeney TM, Jicha DL, Yannelli JR, Martin GR, Kleinman HK: Enhanced tumor growth of both primary and established human and murine tumor cells in athymic mice after coinjection with matrigel. J Natl Cancer Inst 83: 769–774, 1991

    Google Scholar 

  32. Passaniti A, Adler SH, Martin GR: New models to define factors determining the growth and spread of human prostate cancer. J Gerontology, in press, 1991

  33. Stack S, Gray RD, Pizzo SV: Modulation of plasminogen activation and type IV collagenase activity by a synthetic peptide derived from the laminin A chain. Biochem 30: 2073–2077, 1991

    Google Scholar 

  34. McCarthy JB, Palm SL, Furcht LT: Migration of haptotaxis of a Schwann cell tumor line to the basement membrane glycoprotein laminin. J Cell Biol 97: 772–777, 1983

    Google Scholar 

  35. Terranova VP, Aumailley M, Sultan LH, Martin GR, Kleinman HK: Regulation of cell attachment and cell number by fibronectin and laminin. J Cellul Physiol 127: 473–497, 1986

    Google Scholar 

  36. Panayotou G, End P, Aumailley M, Timpl R, Engel J: Domains of laminin with growth factor activity. Cell 56: 93–101, 1989

    Google Scholar 

  37. Hunter DD, Shah V, Merlie JP, Sanes JR: A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction. Nature (London) 338: 229–234, 1989

    Google Scholar 

  38. Aratani Y, Kitagawa Y: Enhanced synthesis and secretion of type IV collagen and entactin during adipose conversion of 3T3-L1 cells and production of unorthodox laminin complex. J Biol Chem 263: 16163–16169, 1988

    Google Scholar 

  39. Ohno M, Martinez-Hernandez A, Ohno N, Kefalides NA: Isolation of laminin from human placental basement membranes: amnion, chorion, and chorionic microvessels. Biochem Biophys Res Commun 112: 1091–1098, 1983

    Google Scholar 

  40. Edgar D, Timpl R, Thoenen H: Structural requirements for the stimulation of neurite outgrowth by two variants of laminin and their inhibition by antibodies. J Cell Biol 106: 1299–1306, 1988

    Google Scholar 

  41. Engvall E, Earvicker D, Haaparanta T, Roushahti E, Sanes JR: Distribution and isolation of four laminin variants; tissue restricted distribution of heterotrimers assembled from five different subunits. Cell Regulation 1: 731–740, 1990

    Google Scholar 

  42. Graf J, Iwamoto Y, Sasaki M, Martin GR, Kleinman HK, Robey FA, Yamada Y: Identification of an amino acid sequence in laminin mediating cell attachment, chemotaxis and receptor binding. Cell 48: 989–996, 1987

    Google Scholar 

  43. Iwamoto Y, Robey FA, Graf J, Sasaki M, Kleinman HK, Yamada Y, Martin GR: YIGSR a pentapeptide from the B1 chain of laminin inhibits tumor cell metastases. Science 238: 1132–1143, 1987

    Google Scholar 

  44. Saiki I, Murata J, Iida J, Nishi N, Sugimura K, Azuma I: The inhibition of murine lung metastases by synthetic polypeptides, [poly (arg-gly-asp) and poly (tyr-ile-gly-ser-arg)] with a core sequence of cell adhesion molecules. Br J Cancer 59: 194–197, 1989

    Google Scholar 

  45. Murata J, Saiki I, Azuma I, Nishi N: Inhibitory effect of a synthetic polypeptide, poly (tyr-ile-gly-ser-arg) on the metastatic formation of malignant tumor cells. Int J Biol Macromol 11: 97–99, 1989

    Google Scholar 

  46. Saiki I, Murata J, Iida J, Sakurai T, Nishi N, Natsuno K, Azuma I: Antimetastatic effects of synthetic polypeptides containing repeated structures of the cell adhesive arg-gly-asp (RGD) and tyr-ile-gly-ser-arg (YIGSR) sequences. Br J Cancer 60: 722–728, 1989

    Google Scholar 

  47. Alino SF, Unda FJ, Perez-Yarza G: Laminin surface binding sites and metastatic potential of 3LL tumor cells by indomethacin. Biochem Biophys Res Commun 167: 731–738, 1990

    Google Scholar 

  48. Sakamoto N, Iwahana M, Tanaka NG, Osada Y: Inhibition of angiogenesis and tumor growth by a synthetic laminin peptide CDPGYIGSR-NH2. Cancer Res 51: 903–906, 1991

    Google Scholar 

  49. Kawasaki K, Namikawa M, Murakami T, Mizuta H, Iwai Y, Hama T, Mayaumi T: Amino acids and peptides XIV. Laminin related peptides and their inhibitory effect on metastasis formation. Biochem Biophys Res Commun 174: 1159–1162, 1991

    Google Scholar 

  50. Kleinman HK, Graf J, Iwamoto Y, Sasaki M, Schasteen CS, Yamada Y, Martin GR, Robey FA: Identification of a second active site in laminin for promotion of cell adhesion, migration, and inhibition of in vivo melanoma lung colonization. Archives Biochem Biophys 272: 39–45, 1989

    Google Scholar 

  51. Charonis A, Skubitz APN, Kohakos GG, Reger LA, Dege J, Vogel AM, Wohlheuter R, Furcht LT: A novel synthetic peptide from the B1 chain of laminin with heparin-binding and cell adhesion promoting activities. J Cell Biol 107: 1253–1260, 1988

    Google Scholar 

  52. Skubitz APN, McCarthy JB, Zhao Q, Yi X-y, Furcht LT: Definition of a sequence, RYVVLPR, within laminin peptide F-9 that mediates metastatic fibrosarcoma cell adhesion and spreading. Cancer Res 50: 7612–7622, 1990

    Google Scholar 

  53. Daneker GW, Piazza AJ, Steele GD, Mercurio AM: Relationship between extracellular matrix interactions and degree of differentiation of human colon carcinoma cell lines. Cancer Res 49: 681–686, 1989

    Google Scholar 

  54. Iwamoto Y, Graf J, Sasaki M, Kleinman HK, Martin GR, Robey FA, Yamada Y: A synthetic pentapeptide from the B1 chain of laminin is chemotactic for B16F10 melanoma cells. J Cellul Physiol 107: 1589–1597, 1988

    Google Scholar 

  55. Kubota Y, Kleinman HK, Martin GR, Lawley TJ: Role of laminin and basement membrane in the differentiation of human endothelial cells into capillary-like structures. J Cell Biol 107: 1589–1597, 1988

    Google Scholar 

  56. Grant DS, Tashiro K, Segui-Real B, Yamada Y, Martin GR, Kleinman HK: Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures. Cell 58: 933–943, 1989

    Google Scholar 

  57. Tashiro K, Sephel GC, Weeks B, Sasaki M, Martin GR, Kleinman HK, Yamada Y: A synthetic peptide containing IKVAV sequence in the A chain of laminin mediated cell attachment, migration, and neurite outgrowth. J Biol Chem 264: 16174–16182, 1989

    Google Scholar 

  58. Kanemoto T, Reich R, Greatorex D, Adler SH, Yamada Y, Kleinman HK: Identification of an amino acid sequence from the laminin A chain which stimulates metastatis formation and collagenase IV production. Proc Natl Acad Sci USA 87: 2279–2283, 1990

    Google Scholar 

  59. Grant DS, Kinsella JL, Fridman R, Piasecki BA, Yamada Y, Zain M, Kleinman HK: Induction of angiogenic behavior by a synthetic peptide from a sequence (SIKVAV) in the laminin A chain. Submitted, 1991

  60. Fidler IJ: General considerations for studies of experimental cancer metastasis. Methods Cancer Res 15: 399–439, 1978

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA

    Thomas M. Sweeney, Maura C. Kibbey, Mona Zain & Hynda K. Kleinman

  2. Molecular Oncology, Inc., 19 Firstfield Rd., Gaithersburg, Maryland, USA

    Rafael Fridman

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  1. Thomas M. Sweeney
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  5. Hynda K. Kleinman
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Sweeney, T.M., Kibbey, M.C., Zain, M. et al. Basement membrane and the SIKVAV laminin-derived peptide promote tumor growth and metastases. Cancer Metast Rev 10, 245–254 (1991). https://doi.org/10.1007/BF00050795

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