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Inhibition of K1735-M2 melanoma cell invasion in vitro by retinoic acid

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Melanoma cell invasion in vitro was tested by means of confrontation cultures of melanoma multicellular spheroids with rounded fragments of embryonic chick heart tissue. Quantitative determination of invasion was performed using a computerized image analysis program, facilitating the evaluation of the efficacy of potentially anti-invasive compounds. Retinoic acid (RA; 1 µm) considerably impaired K1735-M2 melanoma cell invasion, as demonstrated by various measuring parameters. Parameter TUMAREA, expressing the amount of tumor tissue, indicates a growth inhibitory effect and the invasion parameter STRCSTR shows that after treatment with RA the stromal component was better preserved than in untreated controls. Besides the inhibitory effect of RA on melanoma cell invasion in confrontation cultures, RA increased the dynamics of adhesion of melanoma cells to the extracellular matrix components type I collagen and laminin, and slightly impaired melanoma cell directional migration. Fluorescence microscopy using rhodamine-labeled phalloidin showed that RA also modulated the organization of the actin cytoskeleton by inducing the formation of actin-containing stress fibers. Our data show that 1 µM RA exhibited a pronounced anti-invasive effect on highly metastatic melanoma cells in vitro. Impairment of host tissue degradation, altered adhesion abilities, changes in the actin cytoskeleton, as well as the antiproliferative effect may all account for inhibition of melanoma cell invasion.

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References

  1. Bräuner T and Hülser D-F, 1990, Tumor cell invasion and gap junctional communication. Invasion and Metastasis, 10, 31–48.

    Google Scholar 

  2. Liotta LA, 1986, Tumor invasion and metastasesrole of the extracellular matrix: Rhoads memorial award lecture. Cancer Research, 46, 1–7.

    Google Scholar 

  3. Sträuli P and Haemmerli G, 1984, The role of cancer cell motility in invasion. Cancer Metastasis Reviews, 3, 127–141.

    Google Scholar 

  4. Zimmermann A and Keller HU, 1987, Locomotion of tumor cells as an element of invasion and metastasis. Biomedicine, 41, 337–344.

    Google Scholar 

  5. Drewa G and Schachtschabel DO, 1985, Influence of retinoids on growth and melanin content of Harding-Passey melanoma cells in vitro and B16 transplantable melanoma in vivo. Archiv für Geschwulstforschung, 55, 93–98.

    Google Scholar 

  6. Ng KW, Livesey SA, Collier F, Gummer PR and Martin TJ, 1985, Effect of retinoids on the growth, ultrastructure, and cytoskeletal structures of malignant rat osteoblasts. Cancer Research, 45, 5106–5113.

    Google Scholar 

  7. Rutka JT, De Armond SJ, Giblin J, McCulloch JR, Wilson CB and Rosenblum ML, 1988, Effect of retinoids on the proliferation, morphology and expression of glial fibrillary acidic protein of an anaplastic astrocytoma cell line. International Journal of Cancer, 42, 419–427.

    Google Scholar 

  8. Bracke ME, Van Larebeke NA, Yncke BM and Mareel MM, 1991, Retinoic acid modulates both invasion and plasma-membrane ruffling of MCF-7 human mammary carcinoma cells in vitro. British Journal of Cancer, 63, 867–872.

    Google Scholar 

  9. Schroder EW and Black PH, 1980, Retinoids: tumor preventers or tumor enhancers? Journal of the National Cancer Institute, 65, 671–674.

    Google Scholar 

  10. Mehta PP, Bertram JS and Loewenstein WR, 1989, The actions of retinoids on cellular growth correlate with their actions on gap junctional communications. Journal of Cell Biology, 108, 1053–1065.

    Google Scholar 

  11. Edward M, Gold JA and Mac Kie R, 1989, Modulation of melanoma cell adhesion to basement membrane components by retinoic acid. Journal of Cell Sciences, 93, 155–161.

    Google Scholar 

  12. Thorogood P, Smith L, Nicol A, McGinty R and Garrod D, 1982, Effects of vitamin A on the behaviour of migratory neural crest cells in vitro. Journal of Cell Sciences, 57, 331–350.

    Google Scholar 

  13. Hendrix MJC, Wood WR, Seftor EA, Lotan D, Nakajima M, Misiorowski RL, Seftor REB, Stetler-Stevenson WG, Bevacqua SJ, Liotta LA, Sobel ME, Raz A and Lotan R, 1990, Retinoic acid inhibition of human melanoma cell invasion through a reconstituted basement membrane and its relation to decreases in the expression of proteolytic enzymes and motility factor receptor. Cancer Research, 50, 4121–4130.

    Google Scholar 

  14. Takahashi S and Biempica L, 1985, Effect of vitamin A and dexamethasone on collagen degradation in mouse mammary adenocarcinoma. Cancer Research, 45, 3311–3321.

    Google Scholar 

  15. Lehtonen E, Lehto V-P, Badley RA and Virtanen I, 1983, Formation of vinculin plaques precedes other cytoskeletal changes during retinoic acid-induced teratocarcinoma cell differentiation. Experimental Cell Research, 144, 191–197.

    Google Scholar 

  16. Levine N, Miller RC and Meyskens FL, 1984, Oral isotretinoin therapy: use in a patient with multiple cutaneous squamous cell carcinomas and keratoacanthasuas. Archives of Dermatology, 120, 1215–1217.

    Google Scholar 

  17. Lippman SM, Kessler JF and Meyskens FL Jr, 1987, Retinoids as preventive and therapeutic anticancer agents (part II). Cancer Treatment Reports, 71, 493–515.

    Google Scholar 

  18. Meyskens FL Jr, Levine N and Edwards L, 1986, Role of topical tretinoin in melanoma and dysplastic nevi. Journal of the American Academy of Dermatology, 15, 822–825.

    Google Scholar 

  19. Mareel MM, Kint J and Meyvisch C, 1979, Methods of study of the invasion of malignant C3H-mouse fibroblasts into embryonic chick heart in vitro. Virchows Archiv für Pathologische Anatomie und Physiologie und für Klinische Medizin B: Cell Pathology, 30, 95–111.

    Google Scholar 

  20. Smolle J, Helige C and Tritthart HA, 1992, An image analysis and statistical evaluation program for the assessment of tumor cell invasion in vitro. Analytical Cellular Pathology, 4, 49–57.

    Google Scholar 

  21. Smolle J, Helige C, Soyer H-P, Hoedl S, Popper H, Stettner H, Tritthart HA and Kerl H, 1990, Quantitative evaluation of melanoma cell invasion in three dimensional confrontation cultures in vitro using automated image analysis. Journal of Investigative Dermatology, 94, 114–119.

    Google Scholar 

  22. Talmadge JE and Fidler IJ, 1982, Enhanced metastatic potential of tumor cells harvested from spontaneous metastases of heterogenous murine tumors. Journal of the National Cancer Institute, 69, 975–980.

    Google Scholar 

  23. Strom SC and Michalopoulos G, 1982, Collagen as a substrate for cell growth and differentiation. Methods in Enzymology, 82, 544–555.

    Google Scholar 

  24. Storme G and Mareel MM, 1980, Effect of anticancer agents on directional migration of malignant OH mouse fibroblastic cells in vitro. Cancer Research, 40, 943–948.

    Google Scholar 

  25. Storme G, Mareel MM and De Bruyne G, 1981, Influence of cell number on directional migration of MO4 cells in vitro. Archiv für Geschwulstforschung, 51, 45–50.

    Google Scholar 

  26. Fazely F, Moses DC and Ledinko N, 1985, Effects of retinoids on invasion of organ cultures of chick chorioallantoic membrane by adenovirus transformed cells. In Vitro, 21, 409–414.

    Google Scholar 

  27. Fazely F, Ledinko N and Smith DJ, 1988, Inhibition of retinoids of in vitro invasive ability of human lung carcinoma cells. Anticancer Research, 8, 1387–1392.

    Google Scholar 

  28. McGarvey TW, Silberman S and Persky B, 1990, The effect of butyric acid and retinoic acid on invasion and experimental metastasis of murine melanoma cells. Clinical & Experimental Metastasis 8, 433–448.

    Google Scholar 

  29. Nakajima M, Lotan D, Baig MM, Carralero RM, Wood RW, Hendrix JC and Lotan R, 1989, Inhibition of retinoic acid of type IV collagenolysis and invasion through reconstituted basement membrane by metastatic rat mammary adenocarcinoma cells. Cancer Research, 49, 1698–1706.

    Google Scholar 

  30. McGarvey TW, Silberman S and Persky B, 1989, An all-trans-retinoic acid (RA) and butyric acid (BA) drug treatment study on the in vivo metastatic potential of murine B16a melanoma cells. Journal of Cell Biology, 109, Abstract 1000.

    Google Scholar 

  31. Wood WR, Hendrix MJC and Grimes WJ, 1985, Effects of retinoic acid on melanoma tumor cell invasion. Clinical Research, 33, Abstract 75.

    Google Scholar 

  32. Felix EL, Loyd B and Cohen M, 1975, Inhibition of the growth and development of a transplantable murine melanoma by vitamin A. Science, 189, 886–887.

    Google Scholar 

  33. Schleicher RL, Moon RC, Patel MK and Beattie CW, 1988, Influence of retinoids on growth and metastasis of hamster melanoma in athymic mice. Cancer Research, 48, 1465–1469.

    Google Scholar 

  34. Bracke ME, Castronovo V, Van Cauwenberge RML, Coopman P, Vakaet L Jr, Strojny P, Foidart J-M and Mareel MM, 1987, The anti-invasive flavonoid (+) — catechin binds to laminin and abrogates the effect of laminin on cell morphology and adhesion. Experimental Cell Research, 173, 193–205.

    Google Scholar 

  35. Bracke ME, Van Cauwenberge RB and Mareel MM, 1984, (+) — catechin inhibits the invasion of malignant fibrosarcoma cells into chick heart in vitro. Clinical & Experimental Metastasis, 2, 161–170.

    Google Scholar 

  36. Edward M and Mac Kie RM, 1989, Retinoic acid-induced inhibition of lung colonization and changes in the synthesis and properties of glycosaminoglycans of metastatic B16 melanoma cells. Journal of Cell Sciences, 94, 537–543.

    Google Scholar 

  37. Suh O and Weiss L, 1984, The development of a technique for the morphometric analysis of invasion in cancer. Journal of Theoretical Biology, 107, 547–561.

    Google Scholar 

  38. McGarvey TW and Persky B, 1989, The effects of retinoic acid and butyric acid on in vitro migration by murine B16 cells: a quantitative scanning electron microscopic study. Scanning Microscopy, 3, 591–604.

    Google Scholar 

  39. Yasuda Y, Itoh K, Mizuno N, Konishi H and Tanimura T, 1989, Alterations in migrating cranial neural crest cells in embryos of mice fed retinoic acid. Analytical Cellular Pathology, 4, 49–57.

    Google Scholar 

  40. Lotan R, Amos B, Watanabe H and Raz A, 1992, Suppression of melanoma cell motility factor receptor expression by retinoic acid. Cancer Research, 52, 4878–4884.

    Google Scholar 

  41. Van Larebeke NAF, Bracke ME and Mareel MM, 1992, Invasive epithelial cells show more fast plasma membrane movements than related or parental noninvasive cells. Cytometry, 13, 9–14.

    Google Scholar 

  42. Spiro TR and Mundy GR, 1980, In vitro migration of Walker 256 carcinosarcoma cells: dependence on microtubule and microfilament function. Journal of the National Cancer Institute, 65, 463–467.

    Google Scholar 

  43. Volk T, Geiger B and Raz A, 1984, Motility and adhesive properties of high and low metastatic murine neoplastic cells. Cancer Research, 44, 811–824.

    Google Scholar 

  44. Marshall CJ, Humphryes KC and Pollack RE, 1978, Microfilament bundles, LETS protein and growth control in somatic cell hybrids. Journal of Cell Science, 33, 191–204.

    Google Scholar 

  45. Pollack R, Osborn M and Weber K, 1975, Patterns of organization of actin and myosin in normal and transformed cultured cells. Proceedings of the National Academy of Sciences USA, 72, 994–998.

    Google Scholar 

  46. Lotan R, 1980, Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochimica et Biophysica Acta, 605, 33–91.

    Google Scholar 

  47. Bauer EA, Seltzer JL and Eisen AZ, 1983, Retinoic acid inhibition of collagenase and gelatinase expression in human skin fibroblast cultures. Evidence for a dual mechanism. Journal of Investigative Dermatology, 81, 162–169.

    Google Scholar 

  48. Kono T, Furukawa M, Tanii T, Taniguchi S, Mizuno N, Ishii M and Hamada T, 1991, Effect of retinoic acid on the infiltration of murine melanoma cells into the type I collagen gel. Acta Dermato-Venerologia, 71, 41–44.

    Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology and Venerology, Graz, Austria

    C. Helige, J. Smolle, R. Fink-Puches & H. Kerl

  2. Department of Plant Physiology, University of Graz, Graz, Austria

    G. Zellnig

  3. Department of Ophthalmology, University of Graz, Graz, Austria

    E. Hartmann

  4. Department of Medical Physics and Biophysics, University of Graz, Graz, Austria

    H. A. Tritthart

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  1. C. Helige
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  7. H. A. Tritthart
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Helige, C., Smolle, J., Zellnig, G. et al. Inhibition of K1735-M2 melanoma cell invasion in vitro by retinoic acid. Clin Exp Metast 11, 409–418 (1993). https://doi.org/10.1007/BF00132984

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  • DOI: https://doi.org/10.1007/BF00132984

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