Mediation of wound-related Rous sarcoma virus tumorigenesis by TGF-beta.
In Rous sarcoma virus (RSV)-infected chickens, wounding leads to tumor formation with nearly 100% frequency in tissues that would otherwise remain tumor-free. Identifying molecular mediators of this phenomenon should yield important clues to the mechanisms involved in RSV tumorigenesis. Immunohistochemical staining showed that TGF-beta is present locally shortly after wounding, but not unwounded controls. In addition, subcutaneous administration of recombinant transforming growth factor-beta 1 (TGF-beta 1) could substitute completely for wounding in tumor induction. A treatment protocol of four doses of 800 nanograms of TGF-beta resulted in v-src-expressing tumors with 100% frequency; four doses of only 10 nanograms still led to tumor formation in 80% of the animals. This effect was specific, as other growth factors with suggested roles in wound healing did not elicit the same response. Epidermal growth factor (EGF) or TGF-alpha had no effect, and platelet-derived growth factor (PDGF) or insulin-like growth factor-1 (IGF-1) yielded only occasional tumors after longer latency. TGF-beta release during the wound-healing response may thus be a critical event that creates a conducive environment for RSV tumorigenesis and may act as a cofactor for transformation in this system.
Sieweke
M H
MH
Cell and Molecular Biology Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Thompson
N L
NL
Sporn
M B
MB
Bissell
M J
MJ
D000818:Animals; D000906:Antibodies; D002645:Chickens; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D001357:Sarcoma, Avian / Q000150:complications / Q000473:pathology*; D013552:Swine; D015291:Transforming Growth Factors / Q000032:analysis / Q000494:pharmacology*; D014945:Wound Healing; D014947:Wounds and Injuries / Q000150:complications / Q000473:pathology*
D000906:Antibodies; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors