Skeletal Muscle Phenotypically Converts and Selectively Inhibits Metastatic Cells in Mice

Skeletal muscle is rarely a site of malignant metastasis; the molecular and cellular basis for this rarity is not understood. We report that myogenic cells exert pronounced effects upon co-culture with metastatic melanoma (B16-F10) or carcinoma (LLC1) cells including conversion to the myogenic lineage in vitro and in vivo, as well as inhibition of melanin production in melanoma cells coupled with cytotoxic and cytostatic effects. No effect is seen with non-tumorigenic cells. Tumor suppression assays reveal that the muscle-mediated tumor suppressor effects do not generate resistant clones but function through the down-regulation of the transcription factor MiTF, a master regulator of melanocyte development and a melanoma oncogene. Our findings point to skeletal muscle as a source of therapeutic agents in the treatment of metastatic cancers

Delineation of regions in the extracellular domain of follicle-stimulating hormone receptor involved in hormone binding and signal transduction

PROBLEM: To use antipeptide antibodies to potential surface-oriented regions of the extracellular domain (ECD) of the human follicle-stimulating hormone receptor (hFSHR) to delineate regions involved in FSH binding and FSH-induced signal transduction. METHOD OF STUDY: We developed and characterized antipeptide antibodies to different, potentially surface-oriented regions of the ECD of hFSHR. The ability of these antibodies to recognize the receptor was studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting. The ability to modulate FSH binding and cAMP generation was studied by the radioreceptor assay and in vitro FSH bioassay respectively. RESULTS: Antipeptide antibodies to regions 15-31, 216-235, 285-300 and 327-341 hFSHR inhibited both FSH binding and cAMP production. Regions 15-31 and 216-235 were accessible to their cognate antipeptide antibodies both before and after FSH binding,. while regions 285-300 and 327-341 hFSHR were accessible only prior to FSH binding. CONCLUSIONS: Based on the observations made with respect to accessibility to antipeptide antibodies, ability of antibodies to inhibit FSH binding and the subsequent cAMP generation and kinetics of antibody binding, regions 285-300 and 327-341 hFSHR appear to be the chief FSH-binding sites, while regions 15-31 and 216-235 hFSHR serve as ancillary FSH-binding sites