Anti-tumor action of tumor necrosis factor against Bomirski Ab melanoma in hamsters.
BACKGROUND
Tumor necrosis factor (TNF) is a cytokine able to exert anti-tumor activity in various models and modes of applications. However, the exact mechanism mediating the in vivo anti-tumor effect of TNF has not yet been clarified.


METHODS
The effects of intratumoral injection of rat TNF into hamsters bearing Bomirski Ab amelanotic melanoma, a fast growing tumor of high metastatic potential, were tested. Subcutaneous injections of the anti-angiogenic compound TNP-470 allowed analysis of its influence on the effects of TNF administration.


RESULTS
TNF application resulted in a significant inhibition of tumor growth and changes in metastasis pattern. Accelerated hemorrhagic necrosis was also observed, indicating the effect of the cytokine on tumor vessels. Moreover, the synergistic anti-tumor effect of TNF and anti-angiogenic agent TNP-470 suggested a cooperative activity of both substances on tumor vasculature. Microscopically, the effect of TNF injections was expressed by an increase in the amount of tumor cells with nuclear pyknosis and karryorrhexis. In vitro assays indicated a direct cytotoxic effect of TNF against Ab melanoma cells, most probably as an outcome of apoptosis. Intratumoral application of TNF also caused some modulation of cytokine response in melanoma-bearing hamsters as evidenced by increased levels of IL-6 in blood serum.


CONCLUSIONS
This study established Bomirski Ab melanoma as a useful model for complex analysis of the anti-tumor activity of TNF.
Koszałka
Patrycja
P
Department of Medical Biotechnology, Division of Cell Biology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, Debinki 1, 80-211, Gdańsk, Poland. pkosz@amg.gda.pl
Szmit
Ewa
E
Myśliwski
Andrzej
A
Bigda
Jacek
J
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003510:Cyclohexanes / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000097:blood; D007694:Killer Cells, Natural / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008647:Mesocricetus; D009336:Necrosis; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000517:prevention & control; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D012717:Sesquiterpenes / Q000008:administration & dosage; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D015850:Interleukin-6; D011994:Recombinant Proteins; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D000077609:O-(Chloroacetylcarbamoyl)fumagillol