CYTOKINE PRODUCTION IN 5 TUMOR-CELL LINES WITH ACTIVITY TO INDUCE CANCER CACHEXIA SYNDROME IN NUDE-MICE

To identify the so-called toxohormone, which is a tumor-derived factor with activity to induce cancer cachexia syndrome in tumor-bearing ani mals, 5 human cancer cell lines with this activity were studied for cy tokine production. Tumor cell products with activity to inhibit lipopr otein lipase (LPL) were shown to play an important role in the develop ment of the cancer cachexia syndrome. All culture media conditioned by the 5 cell lines possessed LPL-inhibitory activity. However, the acti vity differed with the cell line. In order to characterize the activit y, we examined whether the cultured cells produced cytokines with acti vity to inhibit LPL. A melanoma cell line, SEKI, and a neuoepithelioma cell Line, NAGAI, were found to express a large amount of leukemia in hibitory factor (LIF) mRNA. Furthermore, both of these cell lines were demonstrated to produce a large amount of LIF protein, and plasma lev els of LIF were extremely elevated in SEKI- and NAGAI-bearing nude mic e, indicating that LIF produced by the tumor cells induced cancer cach exia syndrome in the animals. Thus, LIF fulfills the requirements for a toxohormone, except for suppressive activity on liver catalase. In c ontrast, the mechanisms responsible for cachexia in the MKN-1-, LX-1- and LS180-bearing mice remain unknown. These findings suggest that var ious types of bioactive substances produced by cancer cells could be t oxohormones.