MUSCLE-CELLS PRODUCE A LOW-MOLECULAR-WEIGHT FACTOR WITH ANTICANCER ACTIVITY

The present study describes a new low molecular weight factor released by muscle cells, which inhibits proliferation of tumor cells in vitro and in vivo, is highly specific towards tumor cells, and has no obser vable effect on normal cells' proliferation, What first prompted us to investigate this factor was the observation that tumor metastases are extremely rare in striated muscles, Go-culturing of striated muscle c ells with malignant cells led to marked morphological alterations in t he latter, in contrast to the same cells when incubated without muscle cells, A conditioned medium of striated muscle cells was prepared and its effect tested on a variety of cells, This conditioned medium (CM) inhibited proliferation of tumor cell lines of murine (B16 melanoma, Madison 109 lung carcinoma, MCA-105 sarcoma, ESB lymphoma), or of huma n origin (HTB-38 adenocarcinoma, T47D breast carcinoma, CX1 colon carc inoma), The proliferation of normal cells (bone marrow cells, fetal li ver erythroid cells) was not affected by the CM. Flow cytometric analy sis of B16 melanoma cells following incubation with the CM revealed th at 63% +/- 12 of the cells were in the G(0)/G(1) phase of the cell cyc le, compared to 47.8% +/- 8 of cells incubated with a medium (not cond itioned) only, The activity of the CM and of certain Tractions thereof was also demonstrated in vivo: they prevented tumor growth in mice in oculated intraperitoneally with MCA-105 sarcoma cells, Partial purific ation of the CM revealed that the active component was a non-proteinac eous compound with a molecular weight of about 500 D. The results clea rly suggest that muscle cells produce a low molecular weight factor wh ich can selectively inhibit the proliferation of tumor cells in vitro and in vivo. This factor is neither species nor tumor specific.