Inhibition of metastases by a serum factor associated to concomitant resistance induced by unrelated murine tumors

Murine lung metatases growing undisturbed by the primary tumor were signifi cantly inhibited by the concomitant resistance induced by a secondary subcu taneous implant of two unrelated tumors. Such inhibition was T-independent since it was also observed in nude mice; its full expression was dependent on the presence of the secondary tumor implant and it was exerted on both m acroscopic and microscopic established metastases and not on the process of tumor cell dissemination from the primary tumor. Direct and indirect mecha nisms seemed to be involved, the former affecting the metastatic cells per se by causing a decrease in proliferation and an increase in apoptosis whil e the latter affected neovascularization. These antitumor and antiangiogeni c effects could be attributed to a serum factor induced by the unrelated tu mors generating concomitant resistance. This factor proved to be heat, acid and alkaline resistant and dialysable; it was recovered in an HPLC column with maximum absorption at 215 and 266 nm; it was anionic at neutral pH, ex hibiting free carboxil groups and one or more molecules of tyrosine, with a molecular weight between 870 and 1300 Dalton. Intravenous administration o f this factor significantly inhibited lung metastases, decreasing mitosis a nd increasing apoptosis similar to that observed in the presence of the unr elated tumors.