Erythropoietin stimulates proliferation of human renal carcinoma cells.
BACKGROUND
We reported recently that normal human, rat, and mouse tubular cells express authentic erythropoietin-receptors (EPO-R) through which EPO stimulates mitogenesis. The present study examines whether EPO could elicit such a proliferative and thereby potentially detrimental response in cells of human renal-cell carcinoma (RCC).


METHODS
Nephrectomy samples were screened from patients with RCC (one chromophilic, two clear cell) as well as cell lines of human (Caki-2, 786-0) and mouse (RAG) renal adenocarcinomas for expression of EPO-R transcripts and protein. Cells were further tested for specific 125I-EPO binding and mitogenic response to EPO.


RESULTS
Authentic EPO-R transcripts and protein (approximately 72 kD) were detected in renal tumors and cell lines. Tumors showed low-level EPO expression, while cell lines did not. In cells, specific 125I-EPO binding to a single class of EPO-R (apparent Kd 1. 3 to 1.4 nmol/L, Bmax 2.2 to 2.6 fmol/mg protein) was observed. EPO stimulated cell proliferation dose dependently, and the individual mitogenic effects of either EPO or 10% newborn calf serum were markedly amplified when both were coadministered.


CONCLUSIONS
These data are the first to demonstrate, to our knowledge, that human RCCs express EPO-R message and protein and that receptor activation stimulates their proliferation in vitro. If these mitogenic effects of EPO are also operative in patients with RCC, endogenous EPO or its administration for the treatment of anemia could potentially hasten proliferation of renocellular malignancies.
Division of Nephrology, Veterans Administration and University of Utah Medical Centers, Salt Lake City 84148, USA. Westenfelder@pol.net
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D018262:Adenocarcinoma, Clear Cell; D000740:Anemia / Q000378:metabolism; D000818:Animals; D002292:Carcinoma, Renal Cell; D002455:Cell Division / Q000187:drug effects; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D007680:Kidney Neoplasms; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D006623:von Hippel-Lindau Disease / Q000378:metabolism
D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D008934:Mitogens; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin