Transforming growth factor-beta 1 induction of novel extracellular matrix proteins that trigger resistance to tumor necrosis factor cytotoxicity in murine L929 fibroblasts.

The Journal of Biological Chemistry
N S Chang

Abstract

The molecular basis by which transforming growth factor (TGF)-beta 1 protects certain tumor cells from tumor necrosis factor (TNF) cytotoxicity was investigated. When pretreated, with TGF-beta 1, -beta 2, and -beta 3, murine L929S fibroblasts developed resistance to TNF cytotoxicity. Time course experiments revealed that TGF-beta 1 initially induced both cellular protein-tyrosine phosphorylation and simultaneous secretion of a novel extracellular matrix TNF-resistance triggering (TRT) protein(s), which closely preceded the acquisition of TNF-resistance. TGF-beta 2 and -beta 3 also increased tyrosine phosphorylation. However, both molecules failed to stimulate TRT secretion. The increased levels of phosphorylation, particularly to 9 specific protein tyrosine kinase inhibitor-sensitive cellular proteins, appeared to alter the TNF killing pathway. TGF-beta 1-induced TRT secretion required participation of unknown serum factors. TRT adhered strongly to polystyrene plates and resisted treatment with heat (60 degrees C, 30 min), collagenase, alpha 2-macroglobulin, heparin, antibodies against TGF-beta s, and limited trypsin digestion. Notably, TRT promoted TNF-resistance via activation of tyrosine and serine/threonine kinase functions...Continue Reading

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Citations

Sep 25, 1997·International Journal of Cancer. Journal International Du Cancer·J P ZouM Kafka
Jun 15, 2010·Experimental Biology and Medicine·Jean-Yun ChangNan-Shan Chang
Nov 20, 2002·World Journal of Gastroenterology : WJG·Xin-Hua ZhuYi-Tao Ding
Jun 20, 2003·Annals of the New York Academy of Sciences·Smaira Khera, Nan-Shan Chang
Jan 22, 1998·The American Journal of Physiology·N S Chang
Apr 29, 1998·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M J GerdesD R Rowley

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