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Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [D. D. T., C. G. T.]; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts [L. G. J.]; and Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, New Jersey [D. F. D.]
Our previous studies have demonstrated the production and release of a tumor-derived factor that promoted lipolysis in normal adipocytes. We further demonstrated that this in vitro lipolysis was correlated with the in vivo loss of total carcass lipids induced by the presence of the same tumor. This study identified and isolated this "lipolysis-promoting" factor (LPF), released into the extracellular environment (conditioned media) by the human A375 melanoma cell line, which appears to be responsible for the previously demonstrated induction of in vitro and in vivo lipolytic activity. Unlike previously described non-tumor-derived molecules, such as tumor necrosis factor-
/cachectin, which have been implicated in cancer cachexia, the LPF induces alterations in lipid metabolism similar to those observed in cancer patients. The biochemical nature of human tumor-derived LPF appears to be a heat-stable molecule with an apparent molecular weight of approximately 6000. The lipolysis-promoting activity was trichloroacetic acid precipitable, but not precipitable with protamine sulfate or extractable with chloroform:methanol. Its activity appears to be resistant to enzymatic treatments with protease K, trypsin, Pronase, RNase, and DNase, as well as to periodate oxidation. Immunochemically, LPF appears to be distinct from tumor necrosis factor-
/cachectin. Furthermore, in contrast to the mechanism of action of tumor necrosis factor-
/cachectin, the mechanism of "lipolysis promotion" by LPF appears to be by the induction of cellular lipase activity.
1 Supported by a grant from the NIH (CA50458) and a grant from the American Institute for Cancer Research (27A87)
2 To whom requests for reprints should be addressed, at: Department of Surgical Oncology, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111.
Received 8/ 8/91. Accepted 11/20/91.
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