Transforming growth factor-beta protection of cancer cells against tumor necrosis factor cytotoxicity is counteracted by hyaluronidase (review).

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Citation

Chang NS

Transforming growth factor-beta protection of cancer cells against tumor necrosis factor cytotoxicity is counteracted by hyaluronidase (review).

Int J Mol Med. 1998 Dec;2(6):653-9.

PubMed ID
9850732 [ View in PubMed
]
Abstract

Numerous cancer cells, when exposed to transforming growth factor beta (TGF-beta), become resistant to tumor necrosis factor (TNF) cytotoxicity. Pretreatment of L929 fibroblasts, for example, with TGF-beta isoforms (beta 1, beta 2 and beta 3) for at least 0.5-1 h results in resistance to TNF killing. TGF-beta 1 mediates the following sequential events in L929 cells: i) rapid induction of protein tyrosine-phosphorylation (< 30 min), ii) stimulation of protective protein synthesis and acquisition of TNF resistance (approximately 0.5-1 h), and iii) suppression of I kappa B-alpha expression (1-2 h). Two protective proteins induced by TGF-beta 1 are a 46 kDa extracellular matrix TNF-resistance triggering (TRT) protein and a putative transmembrane anti-apoptotic adhesion protein TIF2 (containing and RGD motif in the extracellular region). Both proteins enable L929 cells to resist TNF killing. Notably, testicular hyaluronidase increases TNF sensitivity in several types of cancer cells, counteracts TGF-beta-mediated TNF-resistance, and suppresses TGF-beta 1 gene expression in L929 cells in a serum-dependent manner. Moreover, hyaluronidase antagonizes TGF-beta-mediated inhibition of epithelial cell growth. Both TGF-beta and hyaluronidase are essential for the progression and invasiveness of breast, prostate and other cancers. Conceivably, a stage-dependent expression, as well as a balanced production, of these proteins is essential for cancer development and self protection against TNF cytotoxicity.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
HyaluronidaseTransforming growth factor beta-1ProteinHumans
Unknown
Inhibitor
Details
Hyaluronidase (human recombinant)Transforming growth factor beta-1ProteinHumans
Unknown
Inhibitor
Details
Hyaluronidase (ovine)Transforming growth factor beta-1ProteinHumans
Unknown
Inhibitor
Details