Autocrine growth promotion by multiple hematopoietic growth factors in the established renal cell carcinoma line KU-19–20

Abstract.

Increasing evidence suggests that paraneoplastic syndrome may be mediated by tumor-related cytokine release, although the specific factors involved remain to be clearly defined. The cancer cells used in the present study were obtained from a 67-year-old man with metastatic renal cell carcinoma in the subcutaneous space who demonstrated marked leukocytosis (37,800/mm³). The primary tumor of the kidney was pathologically diagnosed as renal cell carcinoma consistent with the sarcomatoid type. On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in their cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of GM-CSF, G-CSF, IL-6, and IL-8 concentrations in the culture media were identified by an enzyme-linked immunosorbent assay. Reverse transcriptase polymerase chain reaction (RT-PCR) significantly exhibited marker protein m-RNA expression in cancer cells. In addition, GM-CSF receptor and IL-6 receptor mRNA expression was also demonstrated by RT-PCR. The administration of both IL-6 and GM-CSF induced cell-proliferation activities estimated by both [³H]-thymidine and bromodeoxyuridine labeling. Anti-IL-6 antibody and anti-GM-CSF antibody neutralized the enhanced proliferative activities generated by these cytokines. Our findings indicate that the established renal cancer cell line can be demonstrated by both the production of multiple cytokines and by their promotion of autocrine growth. These cells are thus considered to be useful as an effective model for multipotent differentiated renal cell carcinoma, as well as for studying the mechanisms of action of autocrine growth.