| OBJECTIVE To a substantial extent metastasis is responsible for the death of patients with malignant tumors, which poses a conundrum in the treatment of carcinoma. In search of the truth of metastasis, malignant cells themselves, as well as their target organs and cell to organ interactions, are most generally paid close attention while those with negative effects on metastases other than target organs are pretermitted. There must be a kind of mechanism for the rarity of metastases in organs that seldom engender metastases, which deserves much strenuous study. Unfortunately no further research work has been done in such a converse direction.It is a well established phenomenon in clinical experience and autoptic reports that malignant rumors spread and metastasize in almost all of the body's organs, yet are very rare in voluntary striated muscles despite the fact that skeletal muscle comprises nearly 50% of the total body mass and receives an abundant blood supply. The current literature shows that in the last 120 years, very few cases of tumor metastases in striated muscles have been described. It seems that striated muscle is extremely resistant to metastatic cancer, but the mechanism for the rarity of metastases in skeletal muscle is still not clear.METHODS To study the effects of the microenvironment in skeletal muscles on the proliferation of malignant cells and its significance in the rarity of metastases in skeletal muscles, we have set up a series of experiments. Our observations suggest that skeletal muscle derived tumor suppressor (SMDTS) can inhibit tumor growth both in vitro and in vivo. The SMDTS is constitutively released by muscle cells in the body and thus mayhave a physiological role in preventing tumor cell proliferation.1. Primary culture of new born Wistar rat skeletal muscle cells was established and conditioned medium (MMCM) was prepared. The effects of MMCM on several tumor cell lines, of murine origin(SP2/(KPC12 and Siso-V), or of human origin (A549^ Anip-973, CNE, Ecal09, GLC-82, Hela, KB, NCI-H466,PLA-801C (with low metastatic potential) and PLA-801D (with high metastatic potential)) , were tested by MTT assay in vitro;2. Primary culture of human fetal skeletal muscle cells was established and conditioned medium (HMCM) was prepared. The effects of HMCM on several tumor cell lines, of murine origin (SP2/(K PC 12 and Si8o-V) , or of human origin (A549, Anip-973, CNE, Ecal09, GLC-82, Hela, K562, KB, NCI-H466, PC3, SK-BR, PLA-801C and PLA-801D), were tested by MTT assay, in vitro and in vivo (nude mouse inoculated with A549 subcutaneously in the right shoulder, HMCM injected intraperitoneally every other days and in control non-conditioned RPMI medium injected merely in the meantime);3. The effects of MMCM or HMCM on the proliferation of benign cell line (BHK-21) or of ADM on the proliferation of both malignant and benign cell line(s) were carried out by MTT assay as negative or positive control tests in the meantime.RESULTS When incubated with MMCM or HMCM in vitro, several tumor cells showed a dose-dependent, statistically significant inhibition of MTT uptake to a certain degree (at the concentration 100%, PO.001~0.05) while benign cell (BHK-21) showed no inhibitory effect on MTT uptake. There were no differences between the effect of MMCM or HMCM on murine or human tumor cells. The proliferation of lung giant cell carcinoma with high metastatic potential (PLA-801D) was significantly suppressed even when cultured in highly diluted MMCM or HMCM ( 6.25% of crude MMCM or HMCM) while the strain with low metastatic potential (PLA-801C) was suppressed by MMCM or HMCM only at the concentration of 100%. The crude HMCM injected intraperitoneally every other days was extremely effective in suppressing the growth of tumor foci volume in the mouse previously inoculated with A549 cells as compared to non-conditioned RPMI medium. The above results support the existence of a direct correlation between in vitro and in vivo studies. CONCLUSION Skeletal muscle cells of new...
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