Cited by 217Cancer Cells and MetastasisMelanoma and MAPK PathwaysTGF-β signaling in diseases

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

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Cornil, I, Theodorescu, D, Man, S, Herlyn, M, Jambrosic, J, Kerbel, R S·1991·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.88.14.6028PMC PMC52015

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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.

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Authors: Cornil, I., Theodorescu, D., Man, S., Herlyn, M., Jambrosic, J., & Kerbel, R. S.
Affiliations: Mount Sinai Hospital (CA)
ORCID: Theodorescu, D
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1991-07-15
Volume: 88
Issue: 14
Pages: 6028-6032
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.88.14.6028
PMC: PMC52015
OpenAlex: W2015028428
Cited by: 217
References: 28
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 8 · 2014: 2 · 2013: 5 · 2012: 5
FWCI: 6.47
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: National Institutes of Health (5r01ca044877-08)
U.S. Public Health Service (R0I-42331)
National Cancer Institute (CA-25874, P01CA025874, CA 44877)
Topics: Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords: melanoma, dermal fibroblasts, tumor microenvironment, tumor progression, tumor growth, metastasis, radial growth phase, vertical growth phase, tumor stroma, soluble growth factors, metastatic competence
MeSH terms: Adipose Tissue, Animals, Cattle, Cell Communication, Cell Division, Cells, Cultured, DNA Replication, Endothelium, Vascular, Fibroblasts, Humans, Infant, Newborn, Male, Melanoma, Skin, Skin Physiological Phenomena

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

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