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PMID: 8281611 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Transforming growth factor beta and the cell surface in tumor progression.

Cancer metastasis reviews ·Vol. 12 ·No. 3-4 ·1993-09-00 ·Pages 239-54

Newman MJ

Abstract

Type 1 transforming growth beta (TGF-beta 1) is a multifunctional regulator of cellular differentiation, motility and growth. It is capable of inhibiting or stimulating these processes depending on cell type, cell density, culture conditions and TGF-beta 1 concentration. TGF-beta 1 regulates growth, in part, by inducing the expression and secretion of various types of collagen, which participate in the control of cell adhesion and migration, as well as growth. TGF-beta 1 also regulates cell growth by controlling the response to epidermal growth factor (EGF) and other growth factors, in ways that can either decrease or increase their growth-promoting effects. Alterations in both negative and positive growth responses to TGF-beta 1 play important roles in tumor progression. Loss of sensitivity to growth inhibition by TGF-beta 1 can occur as a result of decreased expression of collagen. Acquisition of sensitivity to growth stimulation, and autocrine transformation by TGF-beta 1, are associated with aberrant EGF receptor regulation. Aberrant growth factor receptor regulation by TGF-beta 1 may be mediated by a protein kinase C (PKC)-dependent pathway which inhibits degradation of growth factor receptor/ligand complexes. The evidence reviewed is consistent with a minimal two-step mechanism for autocrine transformation, which involves production of growth factor and enhanced cellular response as a result of aberrant membrane traffic. Defects in membrane traffic regulation may provide an explanation for common alterations in tumor cell response to both multiple growth inhibitors and growth stimulators, and may also suggest novel approaches to cancer chemotherapy.

MeSH Terms
Animals Cell Division/physiology Cell Membrane/physiology Cell Transformation, Neoplastic Epithelial Cells Fibroblasts/cytology Humans Neoplasms/physiopathology Transforming Growth Factor beta/physiology
Chemicals
Transforming Growth Factor beta
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Newman M J
Oncology Research Program, Sandoz Research Institute, Sandoz Pharmaceuticals Corp, Hanover, NJ 07936.
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Article Info
Journal
Cancer metastasis reviews
Abbr.
Cancer Metastasis Rev
ISSN
0167-7659
DOI
10.1007/BF00665956
Published
1993-09-00
Pages
239-54
Language
English
Region
Netherlands
NLM ID
8605731
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00665956 View journal details
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