Skip to main content
SpringerLink
Log in

The invasive phenotypes

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

The expression of the invasive (I+ or I-) phenotypes determines cancer metastasis (M+ or M- phenotype). The invasive (I+ or I-) phenotypes can be divided according to time and site of expression into subphenotypes, which can be assessed separately. At various sites along the metastatic pathway the expression of the I phenotypes can be accompanined by the presence of uncontrolled growth (G+ phenotype) or its absence (G- phenotype). Various combinations of the I and G phenotypes determine the behaviour of metazoan or parasitic cells under normal, pathological non-neoplastic and neoplastic conditions. Although the G+I+M+ combination correlates with full malignancy, the sequence of events leading to the acquisition of these phenotypes during tumor development is not clear. Conditional invasion in experimental systems indicates that a tumor may be invasive and metastatic when part of its population temporarily expresses the I+ phenotype. These experiments further stress the importance of the tumor-host ecosystem for the regulation of the I phenotypes. As distinct from some parasites, the invasive morphotype of vertebrate cells cannot be simply identified. Nevertheless, within the tumor-host ecosystem morphological correlates of the activities of invasive cells may be recognized. They reflect one or more of the I+ functions, namely: motility; loss of homotypic cell-cell adhesion; establishment of alternative cell-substrate and heterotypic cell-cell adhesion; breakdown of extracellular matrices. These functions are not exclusive for I+ tumor cells, and neither are the molecular markers investigated so far. Oncogene activation leads mainly to G+ expression, and in this way serves as a signal amplifier for the I and M phenotypes. Attractive candidate molecular markers of I phenotypes are: regulators of hydrolase activities; cell-cell adhesion molecules; cell surface receptors. From data presently available, we hypothesize that invasion depends upon the balance between an I+ and an I- pathway, with both pathways being sensitive to stimulation and inhibition.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fidler, IJ: Tumor heterogeneity and the biology of cancer invasion and metastasis. Cancer Res 38: 2651–2660, 1978

    Google Scholar 

  2. Billington, WD: Biology of the trophoblast. In: Bishop, MWH (ed) Advances in Reproductive Physiology, Vol. 5. Logos Press Ltd, U.K., 1971, pp 27–66

    Google Scholar 

  3. Duijvestijn, A, Hamann, A: Mechanisms and regulation of lymphocyte migration. Immunology Today 10: 23–28, 1989

    Google Scholar 

  4. DeBaetselier, P, Roos, E, Brys, L, Remels, L, Gobert, M, Dekegel, D, Segal, S, Feldman, M: Nonmetastatic tumor cells acquire metastatic properties following somatic hybridization with normal cells. Cancer Metast Rev 3: 5–24, 1984

    Google Scholar 

  5. Mareel MM, De Baetselier P, Van Roy FM: Mechanisms of invasion and metastasis. CRC Press Inc. Time Mirror Books, 1991, in press

  6. Isberg, RR, Falkow, S: A single genetic locus encoded by Yersinia pseudotuberculosis permits invasion of cultured animal cells by Escherichia coli K-12. Nature 317: 262–264, 1985

    Google Scholar 

  7. Katz, M, Despommier, DD, Gwadz, R: Parasitic Diseases. Springer-Verlag, New York, 1989

    Google Scholar 

  8. Costa J, Rabson AS: Generalised Kaposi's sarcoma is not a neoplasm. Lancet i: 58, 19839

  9. Nakamura, S, Salahuddin, SZ, Biberfeld, P, Ensoli, B, Markham, PD, Wong-Staal, F, Gallo, RC: Kaposi's sarcoma cells: long-term culture with growth factor from retro-virus-infected CD4+ T cells. Science 242: 426–430, 1988

    Google Scholar 

  10. Salahuddin, CZ, Nakamura, S, Biberfeld, P, Kaplan, MH, Markham, PD, Larsson, L, Gallo, RC: Angiogenic properties of Kaposi's sarcoma-derived cells after long-term culture in vitro. Science 242: 430–433, 1988

    Google Scholar 

  11. Krementz, ET, Cerise, EJ, Foster, DS, Morgan, LRJr: Metastases of undetermined source. Curr Problems in Cancer 4: 1–37, 1979

    Google Scholar 

  12. Zajicek, G: Long survival with micrometastasis. At least 9% of breast cancer patients carry metastases for more than 10 years. The Cancer J 1: 414–415, 1987

    Google Scholar 

  13. VanRoy, FM, Messiaen, L, Liebaut, G, Gao, J, Dragonetti, CH, Fiers, WC, Mareel, MM: Invasiveness and metastatic capability of rat fibroblast-like cells before and after transfection with immortalizing and transforming genes. Cancer Res 46: 4787–4795, 1986

    Google Scholar 

  14. Coopman, P, VanRoy, F, Dragonetti, C, Gao, J, Fiers, W, Meneguzzi, G, Mareel, M: Tumorigenicity, invasiveness and metastatic capability of FR3T3 rat cells before and after transfection with bovine papilloma virus type 1 DNA. Clin Expl Metastasis 7: 69–84, 1989

    Google Scholar 

  15. Van Roy FM, Coopman P, Suffys P, Liebaut G, Vleminckx K, Gao J, Dragonetti CH, Fiers W, Mareel MM: Effect of oncogene transfection or passage in vivo on malignant phenotypes of Rat2 cells. Anticancer Res (in press)

  16. Khokha, R, Waterhouse, P, Yagel, S, Lala, P, Overall, C, Norton, G, Denhardt, J: Oncogenicity conferred on Swiss 3T3 cells by reducing TIMP. Science 243: 947–950, 1989

    Google Scholar 

  17. Meyvisch, C, Storme, GA, Bruyneel, E, Mareel, MM: Invasiveness and tumorigenicity of MO4 mouse fibrosarcoma cells pretreated with microtubule inhibitors. Clin Expl Metastasis 1: 17–28, 1983

    Google Scholar 

  18. Owens, RB, Smith, HS, Hackett, AJ: Epithelial cell cultures from normal glandular tissue of mice. J Natl Cancer Inst 53: 261–269, 1974

    Google Scholar 

  19. Mareel M, Coopman P, Dragonetti C, Fiers W, Gao J, Messiaen L, Van Roy F: Spontaneous and oncogene-mediated acquisition of the invasive phenotype by cells in culture. Tumor progression and Metastasis 179–188, 1988

  20. Krief, P, Saint-Ruf, C, Bracke, M, Boucheix, C, Billard, C, Billard, M, Cassingena, R, Jasmin, C, Mareel, M, Azzarone, B: Acquisition of tumorigenic potential in the human myoepithelial HBL100 cell line is associated with decreased expression of HLA class I, class II and integrin β3 and increased expression of c-myc. Int J Cancer 43: 658–664, 1989

    Google Scholar 

  21. Carloni, G, Paterson, H, Mareel, M, Augery-Bourget, Y, Sahraoui, J, Rubinstein, E, Suarez, H, Azzarone, B: N-ras dependent revertant phenotype in human HT1080 fibrosarcoma cells is associated with loss of proliferation within normal tissues and expression of an adult membrane antigenic phenotype. Oncogene 4: 873–880, 1989

    Google Scholar 

  22. Liotta, LA: Tumor invasion and metastases — Role of the extracellular matrix: Rhoads Memorial Award Lecture. Cancer Res 46: 112–113, 1986

    Google Scholar 

  23. Waghorne, C, Thomas, M, Lagarde, A, Kerbel, RS, Breitman, ME: Genetic evidence for progressive selection and overgrowth of primary tumors by metastatic cell subpopulations. Cancer Res 48: 6109–6114, 1988

    Google Scholar 

  24. DeBaetselier, P, Roos, E, VanHecke, D, Verschaeve, L, Brys, L, Verschueren, H: Syngeneic in vivo passage of the murine BW 5147 lymphoma results in the expression of a stable metastatic phenotype. Int J Cancer 41: 720–726, 1988

    Google Scholar 

  25. Van Hecke D, Verschueren H, De Baetselier P: Identification of T-cell antigens, expressed by metastatic T-cell hybridomas and lymphomas. Int J Cancer (in press)

  26. Cuzin, F, Meneguzzi, G, Binétruy, B, Cerni, C, Connan, G, Grisoni, M, DeLapeyrière, O: Stepwise tumoral progression in rodent fibroblasts transformed with bovine papilloma virus type 1 (BPV1) DNA. In: Howley, PM, Broker, TR (eds) Papillomaviruses: Molecular and Clinical Aspects. Alan R. Liss Inc., New York, 1985, pp 473–486

    Google Scholar 

  27. Cajot, J-F, Sordat, B, Bachmann, F: Human primary colon carcinomas xenografted into nude mice. II. Modulation of tumor plasminogen activator activity by the host tissue environment. J Natl Cancer Inst 77: 1099–1107, 1986

    Google Scholar 

  28. Gabbert, H: Mechanism of tumor invasion: evidence from in vivo observations. Cancer Metastasis Rev 4: 293–309, 1985

    Google Scholar 

  29. Roos, E, Van dePavert, IV: Inhibition of lymphoma invasion and liver metastasis formation by pertussis toxin. Cancer Res 47: 5439–5444, 1987

    Google Scholar 

  30. Verschueren, H, Dekegel, D, DeBaetselier, P: Development of a monolayer invasion assay for the discrimination and isolation of metastatic lymphoma cells. Invasion Metastasis 7: 1–15, 1987

    Google Scholar 

  31. Bauer, EA, Gordon, JM, Reddick, ME, Eisen, AZ: Quantitation and immunocytochemical localization of human skin collagenase in basal cell carcinoma. J Invest Dermatol 89: 363–367, 1977

    Google Scholar 

  32. Welch, DR, Schissel, DJ, Howrey, RP, Aeed, PA: Tumorelicited polymorphonuclear cells, in contrast to ‘normal’ circulating polymorphonuclear cells, stimulate invasive and metastatic potentials of rat mammary adenocarcinoma cells. Proc Natl Acad Sci USA 86: 5859–5863, 1989

    Google Scholar 

  33. Lee, AK: Basement membrane and endothelial antigens: their role in evaluation of tumor invasion and metastasis. In: DeLellis, RA (ed) Advances in Immunohistochemistry. Raven Press, New York, 1988, pp 363–393

    Google Scholar 

  34. Willis, RA: Pathology of Tumors. 3rd Edition. Butterworths, London, 1960

    Google Scholar 

  35. Barr, LC, Carter, RL, Davies, AJS: Encapsulation of tumours as a modified wound healing response. Lancet ii: 135–137, 1988

    Google Scholar 

  36. Mareel, MM, VanRoy, FM, Messiaen, LM, Boghaert, ER, Bruyneel, EA: Qualitative and quantitative analysis of tumour invasion in vivo and in vitro. J Cell Sci Suppl 8: 141–163, 1987

    Google Scholar 

  37. McKerrow, JH, Jones, P, Sage, H, Pino-Heiss, S: Proteinases from invasive larvae of the trematode parasite Schistosoma mansoni degrade connective-tissue and basement-membrane macromolecules. Biochem J 231: 47–51, 1985

    Google Scholar 

  38. Bloom, HJG, Richardson, WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–377, 1957

    Google Scholar 

  39. Mareel, MM: Recent aspects of tumor invasiveness. Int Rev Exp Path 22: 65–129, 1980

    Google Scholar 

  40. Albrechtsen, R, Nielsen, M, Wewer, U, Engvall, E, Ruoslahti, E: Basement membrane changes in breast cancer detected by immunohistochemical staining for laminin. Cancer Res 41: 5076, 1981

    Google Scholar 

  41. Ehrmann, RL, Dwyer, IM, Yavner, D, Hancock, WW: An immunoperoxidase study of laminin and type IV collagen distribution in carcinoma of the cervix and vulva. Obstet Gynecol 72: 257, 1988

    Google Scholar 

  42. Sträuli, P, In-Albon, A, Haemmerli, G: Morphological studies on V2 carcinoma invasion and tumor-associated connective tissue changes in the rabbit mesentery. Cancer Res 43: 5403–6410, 1983

    Google Scholar 

  43. Wood, SJr: Pathogenesis of metastasis formation observed in vivo in the rabbit ear chamber. A M A Arch Pathol 66: 550–568, 1958

    Google Scholar 

  44. Mareel, MM, DeMets, M: Anti-invasive activities of experimental chemotherapeutic agents. Critical Rev Oncol/Hematol 9: 263–303, 1989

    Google Scholar 

  45. Maslow, DE, Goldrosen, MH: Relationship of in vitro cell motility and colonization potential in a mouse colon adenocarcinoma (MCA-38) cell line. Invasion Metastasis 8: 133–142, 1988

    Google Scholar 

  46. Verschueren, H, Dekegel, D, DeBaetselier, P: Difference in motile behavior between lymphoma variants with different invasive and metastatic capabilities. Invasion Metastasis 8: 31–44, 1988

    Google Scholar 

  47. Partin, AW, Schoeniger, JS, Mohler, JL, Coffey, DS: Fourier analysis of cell motility: correlation of motility with metastatic potential. Proc Natl Acad Sci USA 86: 1254–1258, 1989

    Google Scholar 

  48. Taniguchi, S, Tatsuka, 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 

  49. Liotta, LA, Mandler, R, Murano, G, Katz, DA, Gordon, RK, Ching, PK, Schiffmann, E: Tumor cell autocrine motility factor. Proc Natl Acad Sci USA 83: 3302–3306, 1986

    Google Scholar 

  50. Goodman, SL, Vollmers, HP, Birchmeier, W: Control of cell locomotion: Perturbation with an antibody directed against specific glycoproteins. Cell 41: 1029–1038, 1985

    Google Scholar 

  51. Stoker, M, Gherardi, E, Perryman, M, Gray, J: Scatter factor is a fibroblast-derived modulator of epithelial cell motility. Nature 327: 239–242, 1987

    Google Scholar 

  52. Grey, A-M, Schor, AM, Rushton, G, Ellis, I, Schor, SL: Purification of the migration stimulating factor produced by fetal and breast cancer patient fibroblasts. Proc Natl Acad Sci USA 86: 2438–2442, 1989

    Google Scholar 

  53. Bracke, ME, VanCauwenberge, RM-L, Storme, GA, Coopman, P, VanLarebeke, N, Mareel, MM: Action mechanisms of anti-invasive agents. Anticancer Res 6: 1273–1278, 1986

    Google Scholar 

  54. Zimmerman, A, Keller, HU: Locomotion of tumor cells as an element of invasion and metastasis. Biomed Pharmacother 41: 337–344, 1987

    Google Scholar 

  55. Coman, DR: Decreased mutual adhesiveness, a property of cells from squamous cell carcinomas. Cancer Res 4: 625–629, 1944

    Google Scholar 

  56. Auerbach, R, Lu, WC, Pardon, E, Gumkowski, F, Kaminska, G, Kaminski, M: Specificity of adhesion between murine tumor cells and capillary endothelium: an in vitro correlate of preferential metastasis in vivo. Cancer Res 47: 1492–1496, 1987

    Google Scholar 

  57. Behrens, J, Mareel, MM, VanRoy, FM, Birchmeier, W: Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomurulin-mediated cell-cell adhesion. J Cell Biol 108: 2435–2447, 1989

    Google Scholar 

  58. Raz, A, Ben-Ze'ev, A: Cell-contact and-architecture of malignant cells and their relationship to metastasis. Cancer Metastasis Rev 6: 3–21, 1987

    Google Scholar 

  59. Nicolson, GL: Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem 30: 214–220, 1982

    Google Scholar 

  60. Iwamoto, Y, Robey, FA, Graf, J, Sasaki, M, Kleinman, HK, Yamada, Y, Martin, GR: YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science 238: 1132–1134, 1987

    Google Scholar 

  61. Humphries, MJ, Olden, K, Yamada, KM: A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 233: 467, 1986

    Google Scholar 

  62. Chung, DC, Zetter, BR, Brodt, P: Lewis lung carcinoma variants with differing metastatic specificities adhere preferentially to different defined extracellular matrix molecules. Invasion Metastasis 8: 103–117, 1988

    Google Scholar 

  63. Albini, AA, Graf, J, Kitten, GT, Kleinman, HK, Martin, GR, Veillette, A, Lippman, ME: 17β-estradiol regulates and v-Ha-ras transfection constitutively enhances MCF-7 breast cancer cell interactions with basement membrane. Proc Natl Acad Sci USA 83: 8182–8186, 1986

    Google Scholar 

  64. Bracke, ME, Castronovo, V, VanCauwenberge, RML, Coopman, P, Vakaet, LJr, Strojny, P, Foidart, J-M, Mareel, MM: The anti-invasive flavonoid (+)-catechin binds to laminin and abrogates the effect of laminin on cell morphology and adhesion. Exp Cell Res 173: 193–205, 1987

    Google Scholar 

  65. Jones, PA, DeClerck, YA: Extracellular matrix destruction by invasive tumor cells. Cancer Metastasis Rev 1: 289–317, 1982

    Google Scholar 

  66. Zucker, S: A critical appraisal of the role of proteolytic enzymes in cancer invasion: emphasis on tumor surface proteinases. Cancer Invest 6: 219–231, 1988

    Google Scholar 

  67. Tryggvason, K, Höyhtyä, M, Salo, T: Proteolytic degradation of extracellular matrix in tumor invasion. Biochim Biophys Acta 907: 191–217, 1987

    Google Scholar 

  68. Mareel, MM, VanRoy, FM: Are oncogenes involved in invasion and metastasis? Anticancer Res 6: 419–436, 1986

    Google Scholar 

  69. Nicolson, GL: Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res 47: 1473–1487, 1987

    Google Scholar 

  70. Muschel, RJ, McKenna, WG: Oncogenes and tumor progression. Anticancer Res 9: 1395–1406, 1989

    Google Scholar 

  71. Eccles, S: The role of oncogenes in metastasis. Cancer Topics 7: 42–46, 1989

    Google Scholar 

  72. VanRoy, FM, Mareel, MM: Oncogenes and tumor progression: state of the art. In: Schirrmacher, V, Schwartz-Albiez, R (eds) Cancer Metastasis, Springer-Verlag, Berlin, 1990, pp 27–35

    Google Scholar 

  73. Yoshida, K, Hamatani, K, Koide, H, Ikeda, H, Nakamura, N, Akiyama, M, Tsuchiyama, H, Nakayama, E, Shiku, H: Preparation of anti-ras Mr 21,000 protein monoclonal antibodies and immunohistochemical analyses on expression of ras genes in human stomach and thyroid cancers. Cancer Res 48: 5503–5509, 1988

    Google Scholar 

  74. Vogelstein, B, Fearon, ER, Hamilton, ST et al: Genetic alterations during colorectal-tumor development. N Engl J Med 319: 525–532, 1988

    Google Scholar 

  75. Bos, JL: Ras oncogenes in human cancer: a review. Cancer Res 49: 4682–4689, 1989

    Google Scholar 

  76. Balmain, A, Ramsden, M, Bowden, GT, Smith, J: Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 307: 658–660, 1984

    Google Scholar 

  77. Brown, K, Quintanilla, M, Ramsden, M, Kerr, IB, Young, S, Balmain, A: v-ras genes from Harvey and BALB murine sacroma viruses can act as initiators of two-stage mouse skin carcinogenesis. Cell 46: 447–456, 1986

    Google Scholar 

  78. Egan, SE, Wright, JA, Jarolim, L, Yanagihara, K, Bassin, RH, Greenberg, AH: Transformation by oncogenes encoding protein kinases induces the metastatic phenotype. Science 238: 202–205, 1987

    Google Scholar 

  79. Collard, JG, Roos, E, LaRivière, G, Habets, GGM: Genetic analysis of invasion and metastasis. Cancer Surveys 7: 691–710, 1988

    Google Scholar 

  80. Pohl, J, Radler-Pohl, A, Schirrmacher, V: A model to account for the effects of oncogenes, TPA, and retinoic acid on the regulation of genes involved in metastases. Cancer Metastasis Rev 7: 347–356, 1988

    Google Scholar 

  81. Kerbel, RS, Waghorne, C, Man, MS, Elliott, B, Breitman, ML: Alteration of the tumorigenic and metastatic properties of neoplastic cells is associated with the process of calcium phosphate-mediated DNA transfection. Proc Natl Acad Sci USA 84: 1263–1267, 1987

    Google Scholar 

  82. Dano, K, Andreasen, PA, Grondahl-Hansen, J, Kristensen, P, Nielsen, LS, Skriver, L: Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 44: 139–266, 1985

    Google Scholar 

  83. Murphy, G, Reynolds, JJ, Hembry, FM: Metalloproteinases and cancer invasion and metastasis. Int J Cancer 44: 757–760, 1989

    Google Scholar 

  84. Baici, A, Knöpfel, M, Keist, R: Tumor-host interactions in the rabbit V2 carcinoma: stimulation of cathepsin B in host fibroblasts by a tumor-derived cytokine. Invasion Metastasis 8: 143–158, 1988

    Google Scholar 

  85. Nakijama, M, Irimura, T, Nicolson, GL: Heparanases and tumor metastasis. J Cell Biochem 36: 157–167, 1988

    Google Scholar 

  86. Mignatti, P, Robbins, E, Rifkin, DB: Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell 47: 487–489, 1986

    Google Scholar 

  87. Ossowski, L: In vivo invasion of modified chorioallantoic membrane by tumor cells: the role of cell surface-bound urokinase. J Cell Biol 107: 2437–2445, 1988

    Google Scholar 

  88. Burtin, P, Fondaneche, M-C: Receptor for plasmin on human carcinoma cells. J Natl Cancer Inst 80: 762–765, 1988

    Google Scholar 

  89. Stephens, RW, Pöllänen, J, Tapiovaara, H, Leung, K-C, Sim, P-S, Salonen, E-M, Ronne, E, Behrendt, N, Dano, K, Vaheri, A: Activation of pro-urokinase and plasminogen on human sarcoma cells: a proteolytic system with surface-bound reactants. J Cell Biol 108: 1987–1995, 1989

    Google Scholar 

  90. Blasi, F, Vassalli, J-D, Dano, K: Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol 104: 801–804, 1987

    Google Scholar 

  91. Schultz, RM, Silberman, S, Persky, B, Bajkowski, AS, Carmichael, DF: Inhibition by human recombinant tissue inhibitor of metalloproteinases of human amnion invasion and lung colonization by murine B16-F10 melanoma cells. Cancer Res 48: 5539–5545, 1988

    Google Scholar 

  92. Takeichi, M, Yoshida-Noro, C, Shirayoshi, Y, Hatta, K: Calcium-dependent cell-cell adhesion system: its molecular nature, cell type specificity, and morphogenetic role. In: Edelman, GM, Thiery, J-P (eds) The Cell in Contact. John Wiley & Sons Inc. New York, 1985, pp 219–232

    Google Scholar 

  93. Gumbiner, B, Stevenson, B, Grimaldi, A: The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol 107: 1575–1587, 1988

    Google Scholar 

  94. Nagafuchi, A, Shirayoshi, Y, Okazaki, K, Yasuda, K, Takeichi, M: Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature 329: 341–343, 1987

    Google Scholar 

  95. Ekblom, P: Determination and differentiation of the nephron. Med Biol (Helsinki) 50: 139–160, 1981

    Google Scholar 

  96. Vestweber, D, Kemler, R: Identification of putative cell adhesion domain of uvomorulin. EMBO J 4: 3393–3398, 1985

    Google Scholar 

  97. Sher, BT, Bargatze, R, Holzmann, B, Gallatin, WM, Matthews, D, Wu, N, Picker, L, Butcher, EC, Weissman, IL: Homing receptors and metastasis. Adv Cancer Res 51: 361–390, 1988

    Google Scholar 

  98. Roossien, FF, deRijk, D, Bikker, A, Roos, E: Involvement of LFA-1 in lymphoma invasion and metastasis demonstrated with LFA-1-deficient mutants. J Cell Biol 108: 1979–1985, 1989

    Google Scholar 

  99. Rice, GE, Bevilacqua, MP: An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science 246: 1303–1306, 1989

    Google Scholar 

  100. Nickoloff, BJ, Griffiths, CEM, Baadsgaard, O, Voorhees, JJ, Hanson, CA, Cooper, KD: Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome. JAMA 261: 2217–2221, 1989

    Google Scholar 

  101. Johnson, JP, Stade, BG, Holzmann, B, Schwäble, W, Riethmüller, G: De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci USA 86: 641–644, 1989

    Google Scholar 

  102. Terranova, VP, Rao, CN, Kalebic, T, Margulies, IM, Liotta, LA: Laminin receptor on human breast carcinoma cells. Proc Natl Acad Sci USA 80: 444–448, 1983

    Google Scholar 

  103. Lissitzky, JC, Bouzon, M, Loret, E, Poupon, MF, Martin, PM: Laminin-mediated adhesion in metastatic rat rhabdomyosarcoma cell lines involves prominent interactions with the laminin E8 fragment. Clin Exp Metastasis 7: 469–480, 1989

    Google Scholar 

  104. Sonnenberg, A, Modderman, PW, Hogervorst, F: Laminin receptor on platelets is the integrin VLA-6. Nature 336: 487–489, 1988

    Google Scholar 

  105. Kleinman, HK, Ogle, RC, Cannon, FB, Little, CD, Sweeney, TM, Luckenbill-Edds, L: Laminin receptors for neurite formation. Proc Natl Acad Sci USA 85: 1282–1286, 1988

    Google Scholar 

  106. Albini, AA, Aukerman, SL, Ogle, RC, Noonan, DM, Fridman, R, Martin, GR, Fidler, IJ: The in vitro invasiveness and interactions with laminin of K-1735 melanoma cells. Evidence for different laminin-binding affinities in high and low metastatic variants. Clin Exp Metastasis 7: 437–451, 1989

    Google Scholar 

  107. Schirrmacher, V, Altevogt, P, Fogel, M, Dennis, J, Waller, CA, Barz, D, Schwartz, R, Cheingsong-Popov, R, Springer, G, Robinson, PG, Nebe, J, Brossmer, W, Vlodavsky, I, Paweletz, N, Zimmerman, H-P, Uhlenbruck, G: Importance of cell surface carbohydrates in cancer cell adhesion, invasion and metastasis. Does sialic acid direct metastatic behavior? Invasion Metastasis 2: 313–360, 1982

    Google Scholar 

  108. Smets, LA, VanBeek, WP: Carbohydrates of the tumor cell surface. Biochim Biophys Acta 738: 237–249, 1984

    Google Scholar 

  109. Bolscher, JGM, Schallier, DCC, Smets, LA, VanRooy, H, Collard, JG, Bruyneel, EA, Mareel, MMK: Effects of cancer-related and drug-induced alterations in surface carbohydrates on the invasive capacity of mouse and rat cells. Cancer Res 46: 4080–4086, 1986

    Google Scholar 

  110. Bolscher, JGM, Schallier, DCC, VanRooy, H, Storme, GA, Smets, LA: Modification of cell surface carbohydrates and invasive behavior by an alkyllysophospholipid. Cancer Res 48: 977–982, 1988

    Google Scholar 

  111. Bruyneel, EA, Debray, H, DeMets, M, Mareel, MM, Montreuil, J: Altered glycosylation in Madin-Darby canine kidney (MDCK) cells after transformation by murine sarcoma virus. Clin Expl Metastasis 8: 241–253, 1990

    Google Scholar 

  112. Bruyneel, EA, DeMets, M, Dragonetti, CH, Hooghe, RJ, DiVirgilio, S, Mareel, MM: Effect of glycosylation inhibitors on N-glycosylpeptides and on invasion of malignant mouse MO4 cells in vitro. J Cell Sci 95: 279–286, 1990

    Google Scholar 

  113. Vakaet, L: The initiation of gastrular ingression in the chick blastoderm. Amer Zool 24: 555–562, 1984

    Google Scholar 

  114. Bellairs, R, VanPeteghem, MC: Gastrulation: is it analogous to malignant invasion? Amer Zool 24: 563–570, 1984

    Google Scholar 

  115. Armstrong, PB: Invasiveness of non-malignant cells. In: Mareel, MM, Calman, KC (eds) Invasion. Experimental and Clinical Implications. Oxford University Press, Oxford, 1984, pp 126–167

    Google Scholar 

  116. Arkin, CF, Millard, M, Medeiros, J: Giant invasive cholesteatoma. Arch Pathol Lab Med 109: 960, 1985

    Google Scholar 

  117. Taylor, HB, Norris, HJ: Epithelial invasion of nerves in benign diseases of the breast. Cancer 20: 2245, 1967

    Google Scholar 

  118. Gabbiani, G: The myofibroblast: a key cell for wound healing and fibrocontractive diseases. In: Deyl, Z, Adam, M (eds) Connective Tissue Research: Chemistry, Biology and Physiology. Alan R. Liss, New York, 1981, pp 183–194

    Google Scholar 

  119. Cairns, J: Cancer. Science and Society. W.H. Freeman and Company, San Francisco, 1978

    Google Scholar 

  120. Sherbet GV: The Metastatic Spread of Cancer. Macmillan Press Ltd., 1987

  121. Dvoretzky, I, Fisher, BK, Haker, O: Mutilating basal cell epithelioma. Arch Dermat 114: 2496250, 1978

    Google Scholar 

  122. Mareel, MM, DeMets, M: Effect of microtubule inhibitors on invasion and on related activities of tumor cells. Int Rev Cytol 90: 125–167, 1984

    Google Scholar 

  123. Bracke, ME, VanCauwenberge, RM-L, Mareel, MM: (+)-Catechin inhibits the invasion of malignant fibrosarcoma cells into chick heart in vitro. Clin Expl Metastasis 2: 161–170, 1984

    Google Scholar 

  124. Storme, GA, Bruyneel, EA, Schallier, DC, Bolscher, JG, Berdel, BE, Mareel, MM: Effect of lipid derivatives on invasion in vitro and on surface glycoproteins of three rodent cell types. Lipids 22: 847–850, 1987

    Google Scholar 

  125. Storme, G, Mareel, MM: Effect of anticancer agents on invasion of mouse fibrosarcoma cells in vitro. Oncology 38: 182–186, 1981

    Google Scholar 

  126. Scher, HI, Yagoda, A: Bone metastases: pathogenesis, treatment, and rationale for use of resorption inhibitors. Am J Med 82: 6–28, 1987

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory for Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, State University of Ghent, Ghent

    Marc M. Mareel

  2. Laboratory of Molecular Biology, State University of Ghent, Ghent

    Frans M. Van Roy

  3. Institute of Molecular Biology, Free University of Brussels, Brussels, Belgium

    Patrick De Baetselier

Authors
  1. Marc M. Mareel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frans M. Van Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick De Baetselier
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mareel, M.M., Van Roy, F.M. & De Baetselier, P. The invasive phenotypes. Cancer Metast Rev 9, 45–62 (1990). https://doi.org/10.1007/BF00047588

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00047588

Key words

Search

Navigation