Expression of the TNF-alpha gene on mouse lung carcinoma cells suppresses spontaneous lung metastasis without affecting tumorigenicity.
Forced expression of TNF-alpha in tumor cells has been shown to inhibit their tumor growth in vivo through a number of mechanism such as activation of an immune system and induction of an apoptotic process. We re-examined the anti-tumor effects caused by the TNF-alpha gene transfer using high-metastatic, murine lung carcinoma A11 cells. Expressed TNF-alpha molecules remained on cell surface and were not secreted into culture supernatants in vitro. Syngeneic immunocompetent mice developed tumors of TNF-alpha-expressed A11 cells and the growth of their subcutaneous tumors was not different from that of parent tumors. Spleen of the mice that developed TNF-alpha-expressed A11 tumors was significantly larger than that of the mice bearing parent tumors, but relative ratios of each cell population were not different. In contrast to subcutaneous tumors, the number of spontaneous lung foci metastasized from the subcutaneous TNF-alpha-expressed A11 tumors was markedly reduced compared with that from parent tumors. Expressed TNF-alpha on tumors is released by matrix metalloproteinases from surrounding tissues and anti-tumor effects by TNF-alpha can be influenced by local environmental conditions.
Tada
Yuji
Y
Division of Pathology, Chiba Cancer Center Research Institute, Chuo-ku, Chiba 260-8717, Japan.
O-Wang
Jiyang
J
Takenaga
Keizo
K
Takiguchi
Yuichi
Y
Tatsumi
Koichiro
K
Kuriyama
Takayuki
T
Tagawa
Masatoshi
M
D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D002455:Cell Division; D005434:Flow Cytometry; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control; D013154:Spleen / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha