Secretion of autocrine growth-promoting activity by renal-carcinoma cells treated with 5-fluorouracil.
A study was made of the auto-proliferative activity of human renal-carcinoma cells in the supernatant from a carcinoma-cell culture in serum-free medium to which an anticancer agent had been added (5-FU). The human renal-cancer cells used in this study were of 3 strains: ACHN, VMRC-RCW and NT. When each line was cultured in medium containing no 5-FU, the supernatant showed almost no activity for stimulating DNA synthesis. However, when the line was cultured in the presence of 5-FU, the supernatant showed autocrine growth-promoting activity which strongly stimulated DNA synthesis of 3 renal-cancer cell lines in a dose-dependent manner. Activity could be detected in a 4- to 6-kDa fraction by gel filtration. This fraction increased the DNA-synthesis-promoting activity of epidermal growth factor, transforming growth factor-beta, basic fibroblast growth factor and insulin, and was acid- and heat-stable. It was also stable against pepsin and dithiothreitol. DNA synthesis in BALB/c 3T3, adult rat hepatocytes and rabbit renal tubular cells was not affected by this fraction which was thus considered not to affect non-cancerous cells. Renal-cell carcinoma responds poorly to anticancer agents, and the autocrine activity of the fraction may possibly be a factor accounting for this resistance.
Nishimura
N
N
Department of Urology, Nagasaki University School of Medicine, Japan.
Kanda
S
S
Yogi
Y
Y
Kawamura
M
M
Nakamura
M
M
Hyakutake
H
H
Kanetake
H
H
Saito
Y
Y
D016475:3T3 Cells; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005472:Fluorouracil / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D006133:Growth Substances; D005472:Fluorouracil