Constitutive and IFN-gamma regulated expression of IL-7 and IL-15 in human renal cell cancer.
Although not structurally related, the pleiotropic cytokines interleukin-7 (IL-7) and interleukin-15 (IL-15) share a variety of biological functions including stimulation and maintenance of cellular immune responses. Cytokines, such as IL-7 or IL-15, elaborated by cells in situ, e.g. cancer cells, may be involved in shaping the quality of anti-tumor directed immune responses. We have analysed the constitutive and IFN-gamma-inducible expression of IL-15 or IL-7 mRNA, protein expression, and protein secretion in human tumor cell lines of distinct origin. IL-15 mRNA expression was detected in renal cell carcinoma (RCC), small cell lung carcinoma (SCLC), glioblastoma, neuroblastoma, mesothelioma cells and in EBV-transformed B-lymphocytes. IL-7-specific transcripts could be detected in colorectal cancer and in renal cell cancer cell lines. Immunohistochemical analysis demonstrated cytosolic IL-15 protein expression in renal cell cancer cells without apparent IL-15 protein secretion in vitro. Time kinetic analyses revealed that IFN-gamma mediated increase of IL-15 mRNA expression was transcriptionally regulated and dependent on de novo protein synthesis. However, enhanced IL-15 mRNA expression did not lead to effective protein secretion. In contrast, IL-7 mRNA expression in renal cell cancer or in colorectal cancer was associated with effective protein secretion which could be augmented by IFNgamma-treatment. These data suggest that both IL-7 and IL-15 mRNA are expressed in renal cell cancer, but exclusively IL-7 may be elaborated by tumor cells in situ. IL-15 regulation appears to be tightly controlled both at the transciptional and post-transcriptional level. Appropriate stimuli leading to effective IL-15 secretion from tumor cells may aid in modulating cellular immune responses directed against cancer.
Trinder
P
P
Department of Medical Microbiology, Johannes Gutenberg University of Mainz, Mainz, Germany.
Seitzer
U
U
Gerdes
J
J
Seliger
B
B
Maeurer
M
M
D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D015851:Interleukin-7 / Q000235:genetics* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D019409:Interleukin-15; D015851:Interleukin-7; D012333:RNA, Messenger; D007371:Interferon-gamma