TY - JOUR
T1 - Muscle cells produce a low molecular weight factor with anti-cancer activity
AU - Djaldetti, Meir
AU - Sredni, Benjamin
AU - Zigelman, Rosa
AU - Verber, Moshe
AU - Fishman, Pnina
PY - 1996
Y1 - 1996
N2 - The present study describes a new low molecular weight factor released by muscle cells, which inhibits proliferation of tumor cells in vitro a 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 (GM) 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 GM. 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 GM 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 GM 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.
AB - The present study describes a new low molecular weight factor released by muscle cells, which inhibits proliferation of tumor cells in vitro a 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 (GM) 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 GM. 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 GM 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 GM 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.
KW - Inhibition
KW - Muscle factor
KW - Proliferation
KW - Tumor cells
UR - http://www.scopus.com/inward/record.url?scp=0030017725&partnerID=8YFLogxK
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C2 - 8674272
AN - SCOPUS:0030017725
SN - 0262-0898
VL - 14
SP - 189
EP - 196
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 3
ER -