• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jul 15, 1991; 88(14): 6028–6032.
PMCID: PMC52015

Fibroblast cell interactions with human melanoma cells affect tumor cell growth as a function of tumor progression.

Abstract

It is known from a variety of experimental systems that the ability of tumor cells to grow locally and metastasize can be affected by the presence of adjacent normal tissues and cells, particularly mesenchymally derived stromal cells such as fibroblasts. However, the comparative influence of such normal cell-tumor cell interactions on tumor behavior has not been thoroughly investigated from the perspective of different stages of tumor progression. To address this question we assessed the influence of normal dermal fibroblasts on the growth of human melanoma cells obtained from different stages of tumor progression. We found that the in vitro growth of most (4 out of 5) melanoma cell lines derived from early-stage radial growth phase or vertical growth phase metastatically incompetent primary lesions is repressed by coculture with normal dermal fibroblasts, suggesting that negative homeostatic growth controls are still operative on melanoma cells from early stages of disease. On the other hand, 9 out of 11 melanoma cell lines derived from advanced metastatically competent vertical growth phase primary lesions, or from distant metastases, were found to be consistently stimulated to grow in the presence of dermal fibroblasts. Evidence was obtained to show that this discriminatory fibroblastic influence is mediated by soluble inhibitory and stimulatory growth factor(s). Taken together, these results indicate that fibroblast-derived signals can have antithetical growth effects on metastatic versus metastatically incompetent tumor subpopulations. This resultant conversion in responsiveness to host tissue environmental factors may confer upon small numbers of metastatically competent cells a growth advantage, allowing them to escape local growth constraints both in the primary tumor site and at distant ectopic tissue sites.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cunha GR, Bigsby RM, Cooke PS, Sugimura Y. Stromal-epithelial interactions in adult organs. Cell Differ. 1985 Sep;17(3):137–148. [PubMed]
  • Dotto GP, Moellmann G, Ghosh S, Edwards M, Halaban R. Transformation of murine melanocytes by basic fibroblast growth factor cDNA and oncogenes and selective suppression of the transformed phenotype in a reconstituted cutaneous environment. J Cell Biol. 1989 Dec;109(6 Pt 1):3115–3128. [PMC free article] [PubMed]
  • Dotto GP, Weinberg RA, Ariza A. Malignant transformation of mouse primary keratinocytes by Harvey sarcoma virus and its modulation by surrounding normal cells. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6389–6393. [PMC free article] [PubMed]
  • Gerschenson M, Graves K, Carson SD, Wells RS, Pierce GB. Regulation of melanoma by the embryonic skin. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7307–7310. [PMC free article] [PubMed]
  • La Rocca SA, Grossi M, Falcone G, Alemà S, Tatò F. Interaction with normal cells suppresses the transformed phenotype of v-myc-transformed quail muscle cells. Cell. 1989 Jul 14;58(1):123–131. [PubMed]
  • Dotto GP, Parada LF, Weinberg RA. Specific growth response of ras-transformed embryo fibroblasts to tumour promoters. Nature. 1985 Dec 5;318(6045):472–475. [PubMed]
  • Farber E, Cameron R. The sequential analysis of cancer development. Adv Cancer Res. 1980;31:125–226. [PubMed]
  • Herlyn M, Kath R, Williams N, Valyi-Nagy I, Rodeck U. Growth-regulatory factors for normal, premalignant, and malignant human cells in vitro. Adv Cancer Res. 1990;54:213–234. [PubMed]
  • Chadwick DE, Lagarde AE. Coincidental acquisition of growth autonomy and metastatic potential during the malignant transformation of factor-dependent CCL39 lung fibroblasts. J Natl Cancer Inst. 1988 May 4;80(5):318–325. [PubMed]
  • Schwarz LC, Gingras MC, Goldberg G, Greenberg AH, Wright JA. Loss of growth factor dependence and conversion of transforming growth factor-beta 1 inhibition to stimulation in metastatic H-ras-transformed murine fibroblasts. Cancer Res. 1988 Dec 15;48(24 Pt 1):6999–7003. [PubMed]
  • Rodeck U, Herlyn M, Menssen HD, Furlanetto RW, Koprowsk H. Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors. Int J Cancer. 1987 Nov 15;40(5):687–690. [PubMed]
  • Cornil I, Man S, Fernandez B, Kerbel RS. Enhanced tumorigenicity, melanogenesis, and metastases of a human malignant melanoma after subdermal implantation in nude mice. J Natl Cancer Inst. 1989 Jun 21;81(12):938–944. [PubMed]
  • Montesano R, Mossaz A, Ryser JE, Orci L, Vassalli P. Leukocyte interleukins induce cultured endothelial cells to produce a highly organized, glycosaminoglycan-rich pericellular matrix. J Cell Biol. 1984 Nov;99(5):1706–1715. [PMC free article] [PubMed]
  • Schor SL, Schor AM, Durning P, Rushton G. Skin fibroblasts obtained from cancer patients display foetal-like migratory behaviour on collagen gels. J Cell Sci. 1985 Feb;73:235–244. [PubMed]
  • Mayer TC. Site of gene action in steel mice: analysis of the pigment defect by mesoderm-ectoderm recombinations. J Exp Zool. 1973 Jun;184(3):345–352. [PubMed]
  • Schor SL, Schor AM. Clonal heterogeneity in fibroblast phenotype: implications for the control of epithelial-mesenchymal interactions. Bioessays. 1987 Nov;7(5):200–204. [PubMed]
  • Gresser I, Tovey MG. Antitumor effects of interferon. Biochim Biophys Acta. 1978 Oct 27;516(2):231–247. [PubMed]
  • Blat C, Chatelain G, Desauty G, Harel L. Inhibitory diffusible factor IDF45, a G1 phase inhibitor. FEBS Lett. 1986 Jul 28;203(2):175–180. [PubMed]
  • Hsu YM, Wang JL. Growth control in cultured 3T3 fibroblasts. V. Purification of an Mr 13,000 polypeptide responsible for growth inhibitory activity. J Cell Biol. 1986 Feb;102(2):362–369. [PMC free article] [PubMed]
  • Kurtz A, Vogel F, Funa K, Heldin CH, Grosse R. Developmental regulation of mammary-derived growth inhibitor expression in bovine mammary tissue. J Cell Biol. 1990 May;110(5):1779–1789. [PMC free article] [PubMed]
  • Swope VB, Abdel-Malek Z, Kassem LM, Nordlund JJ. Interleukins 1 alpha and 6 and tumor necrosis factor-alpha are paracrine inhibitors of human melanocyte proliferation and melanogenesis. J Invest Dermatol. 1991 Feb;96(2):180–185. [PubMed]
  • Whicher JT, Evans SW. Cytokines in disease. Clin Chem. 1990 Jul;36(7):1269–1281. [PubMed]
  • Pritchett TR, Wang JK, Jones PA. Mesenchymal-epithelial interactions between normal and transformed human bladder cells. Cancer Res. 1989 May 15;49(10):2750–2754. [PubMed]
  • Miller FR, Medina D, Heppner GH. Preferential growth of mammary tumors in intact mammary fatpads. Cancer Res. 1981 Oct;41(10):3863–3867. [PubMed]
  • Kerbel RS. Growth dominance of the metastatic cancer cell: cellular and molecular aspects. Adv Cancer Res. 1990;55:87–132. [PubMed]
  • Garin-Chesa P, Old LJ, Rettig WJ. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7235–7239. [PMC free article] [PubMed]
  • Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986 Dec 25;315(26):1650–1659. [PubMed]
  • Klein G. Multistep emancipation of tumors from growth control: can it be curbed in a single step? Bioessays. 1990 Jul;12(7):347–350. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...