%0 Journal Article %J Growth Factors %D 1990 %T Aberrant TGF-beta production and regulation in metastatic malignancy. %A Schwarz, L C %A Wright, J A %A Marie-Claude Gingras %A Kondaiah, P %A Danielpour, D %A Pimentel, M %A Sporn, M B %A Greenberg, A H %K Animals %K Cell Line, Transformed %K Fibrosarcoma %K Gene Expression Regulation, Neoplastic %K Immunohistochemistry %K Lung Neoplasms %K Mice %K Mice, Inbred C3H %K Oncogenes %K Protein Kinases %K Receptors, Cell Surface %K Receptors, Transforming Growth Factor beta %K RNA, Messenger %K Transforming Growth Factor beta %K Tumor Cells, Cultured %X

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.

%B Growth Factors %V 3 %P 115-27 %8 1990 %G eng %N 2 %1 https://www.ncbi.nlm.nih.gov/pubmed/2169772?dopt=Abstract %R 10.3109/08977199009108274