Aberrant TGF-beta production and regulation in metastatic malignancy.

TitleAberrant TGF-beta production and regulation in metastatic malignancy.
Publication TypeJournal Article
Year of Publication1990
AuthorsSchwarz, LC, Wright, JA, Gingras, M-C, Kondaiah, P, Danielpour, D, Pimentel, M, Sporn, MB, Greenberg, AH
JournalGrowth Factors
Date Published1990
KeywordsAnimals, Cell Line, Transformed, Fibrosarcoma, Gene Expression Regulation, Neoplastic, Immunohistochemistry, Lung Neoplasms, Mice, Mice, Inbred C3H, Oncogenes, Protein Kinases, Receptors, Cell Surface, Receptors, Transforming Growth Factor beta, RNA, Messenger, Transforming Growth Factor beta, Tumor Cells, Cultured

We have examined the possible role of transforming growth factor-beta (TGF-beta) in metastatic malignancy by analyzing the production and activation of TGF-beta 1 and -beta 2 and the regulation of TGF-beta-responsive genes in oncogene-transformed metastatic fibrosarcomas. All transformed lines derived from either 10T1/2 or NIH 3T3 by either H-ras or protein-kinase encoding oncogenes produced more TGF-beta than parental cells. However, only highly metastatic fibrosarcomas secreted activated TGF-beta at rates that were greater than parental fibroblasts. Immunohistochemical staining for TGF-beta 1 showed widespread intra- and extracellular distribution in metastatic lung nodules and adjacent tissue. Cells isolated from tumors successfully metastasizing to the lung had TGF-beta 1 mRNA levels which were increased 19-fold over in vitro controls. Despite the greatly enhanced rate of secretion of activated TGF-beta, metastatic cells exhibited markedly altered responses of TGF-beta 1 and TGF-beta 2, being unable to either increase collagen secretion or enhance collagen alpha 2(1) or TGF-beta 1 mRNA levels. This lack of response was not due to either altered TGF-beta receptor affinity or numbers. Metastatic progression was, therefore, associated with an increase in the secretion of activated TGF-beta 1 and a loss of the ability to deregulate TGF-beta-responsive genes.

Alternate JournalGrowth Factors
PubMed ID2169772

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