Muscle cells produce a low molecular weight factor with anti-cancer 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 observable 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. Co-culturing of striated muscle cells with malignant cells led to marked morphological alterations in the 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 human origin (HTB-38 adenocarcinoma, T47D breast carcinoma, CX1 colon carcinoma). The proliferation of normal cells (bone marrow cells, fetal liver erythroid cells) was not affected by the CM. Flow cytometric analysis of B16 melanoma cells following incubation with the CM revealed that 63% +/- 12 of the cells were in the G0/G1 phase of the cell cycle, compared to 47.8% +/- 8 of cells incubated with a medium (not conditioned) only. The activity of the CM and of certain fractions thereof was also demonstrated in vivo: they prevented tumor growth in mice inoculated intraperitoneally with MCA-105 sarcoma cells. Partial purification of the CM revealed that the active component was a non-proteinaceous compound with a molecular weight of about 500 D. The results clearly suggest that muscle cells produce a low molecular weight factor which can selectively inhibit the proliferation of tumor cells in vitro and in vivo. This factor is neither species nor tumor specific.