Erythropoietin stimulates proliferation of human renal carcinoma cells

Kidney Int. 2000 Aug;58(2):647-57. doi: 10.1046/j.1523-1755.2000.00211.x.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma, Clear Cell
  • Anemia / metabolism
  • Animals
  • Carcinoma, Renal Cell*
  • Cell Division / drug effects
  • Erythropoietin / metabolism
  • Erythropoietin / pharmacology*
  • Gene Expression / drug effects
  • Humans
  • Iodine Radioisotopes
  • Kidney Neoplasms*
  • Kidney Tubules, Proximal / cytology*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Mitogens / metabolism
  • Mitogens / pharmacology
  • Neovascularization, Pathologic / metabolism
  • RNA, Messenger / analysis
  • Receptors, Erythropoietin / genetics
  • Receptors, Erythropoietin / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured
  • von Hippel-Lindau Disease / metabolism


  • Iodine Radioisotopes
  • Membrane Proteins
  • Mitogens
  • RNA, Messenger
  • Receptors, Erythropoietin
  • Erythropoietin