Tumor stasis factor (TSF): A possible mechanism for the regulation of tumor cell proliferation

A new class of factors that regulates tumor cell division in vitro can be isolated from fresh and cultured tumor cells by 3 M KCl extraction. Tumor stasis factors (TSF) inhibiting cultured tumor cell proliferation were extracted from 8 of 11 fresh human tumors and 2 cultured tumor cell lines. TSF inhibited [³H]Tdr incorporation by allogeneic and autologous cultured tumor cells in a dose-dependent manner. Extracts of normal human tissues and benign tumors did not demonstrate inhibition with the exception of liver. The mechanism of inhibition was cytostatic and not cytotoxic as demonstrated with trypan blue exclusion by tumor cells following TSF treatment, maintenance of intact tumor cell monolayers following addition of TSF, and lack of inhibition of Con A-mediated lymphocyte proliferation by TSF. TSF activity could be reversed by washing for up to 48 hr of incubation and was resistant to heat, pH alterations, reducing agents, proteases, and glycosidases. However, the active moiety bound to lentil lectin and could be purified 80-fold by preparative isoelectric focusing. These factors may represent a novel regulatory mechanism for tumor cell proliferation.