Tanaka A, Matsuoka H, Uemura H, Kakui Y, Imanishi T, Nishino H, Imanishi J
J Natl Cancer Inst. 1985 Mar;74(3):575-81.
Degenerative changes of human tumor cells or continuous cell lines occur when they are cocultured with human embryonic fibroblasts. The present study confirmed that the degenerative changes of the target cells were due to a factor secreted from the human fibroblast culture, because the culture supernatant of human fibroblast caused the same degenerative changes as those induced by the coculture. This factor was termed "tumor-degenerating factor" (TDF). TDF was produced in the fibroblast culture as early as the 1st day and increased gradually up to the 8th day. TDF induced the degenerative changes in human KB cells, HeLa cells, FL cells, and PLC/PRF/5 cells but not in human WiDr cells or in fibroblasts. Also, it did not induce the degenerative changes in various murine cells, bovine cells, rabbit cells, or monkey cells, suggesting that TDF has species specificity. Furthermore, human leukocyte interferon enhanced the activity of TDF. TDF with the specific activity of 2.9 U/mg protein was purified by several chromatographies. At a final recovery rate of 14.6%, the specific activity was increased to 9,010 U/mg protein. Its molecular weight was estimated about 26,500-30,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. TDF was relatively stable to heat treatment.
人类肿瘤细胞或连续细胞系与人胚胎成纤维细胞共培养时会发生退行性变化。本研究证实，靶细胞的退行性变化是由于人成纤维细胞培养物分泌的一种因子所致，因为人成纤维细胞的培养上清液会引起与共培养诱导的相同的退行性变化。这种因子被称为“肿瘤退行性因子”（TDF）。TDF最早在成纤维细胞培养的第1天产生，并逐渐增加直至第8天。TDF可诱导人KB细胞、HeLa细胞、FL细胞和PLC/PRF/5细胞发生退行性变化，但对人WiDr细胞或成纤维细胞无此作用。此外，它也不会诱导各种鼠细胞、牛细胞、兔细胞或猴细胞发生退行性变化，这表明TDF具有种属特异性。此外，人白细胞干扰素可增强TDF的活性。通过几种色谱法纯化得到了比活性为2.9 U/mg蛋白的TDF。最终回收率为14.6%时，比活性提高到了9010 U/mg蛋白。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳估计其分子量约为26,500-30,000。TDF对热处理相对稳定。
