Lipolytic and lipoprotein lipase (LPL)-inhibiting activities produced by a human lung cancer cell line responsible for cachexia induction.

Previous studies have shown that five human cancer cell lines, LS180, MKN-1, MMG-1, C32 and LX-1, induced remarkable weight loss in tumor-bearing nude mice. With the aim of identifying novel molecules involved in lipid catabolism, conditioned media of these cancer cell lines were analyzed in terms of lipoprotein lipase (LPL)-inhibiting or lipolytic activities. All conditioned media from the five cell lines significantly suppressed LPL activity in 3T3-L1 cells, while media from LX-1 and C32 promoted lipolytic activity in a dose-dependent manner. RT-PCR and ELISA demonstrated that the major factors responsible for LPL inhibition and lipolysis were not IL-1beta, IL-6, IL-11, TNF-alpha, TGF-beta1 or LIF in all the cancer cell lines except for MMG-1 cells. Preliminary biochemical analysis showed that the LPL-inhibiting factor produced by LX-1 cells was approximately 65 kD and vulnerable to heat, whereas the lipolytic factor was less than 1 kD and heat stable. These results suggested that unknown factors are partially involved in the pathogenesis of cancer cachexia in tumor-bearing nude mice and further purification will be needed.