Summary
Recombinant human (rh) erythropoietin (EPO) is attracting increasing interest as an agent for treating cancer-related anemia. Thus, we have tested the effects of rhEPO on the clonal growth of 22 different cell lines derived from a wide range of human solid tumors (head and neck 3, lung 2, breast 2, stomach 1, colorectal 3, hepatocellular 1, pancreas 1, ovary 1, choriocarcinoma 1, osteogenic sarcoma 1, glioblastoma 2, neuroblastoma 1, prostate 1, renal 2) in vitro. RhEPO (dose range 0.01–100 U/ml) caused no significant and reproducible stimulation of clonal growth as measured by a capillary modification of the human tumor cloning assay in agar in any of the cell lines tested. In particular, there was no sensitivity for rhEPO of those cell lines which were shown to be responsive to interleukin-3 and GM-CSF. On the other hand, there were no growth inhibitory effects of rhEPO on the cell lines of this study. Finally, neutralizing anti-human EPO antibody had no effect on the clonal growth of two kidney carcinoma cell lines, making autocrine growth regulation by hEPO in these lines unlikely.
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References
Adamson JW (1989) The promise of recombinant human erythropoietin. Semin Hematol 26: 5–8
Asano Y, Okamura S, Shibuya T, Harada M, Niho Y (1988) Growth of clonogenic myeloblastic leukemia cells in the presence of human recombinant erythropoietin in addition to various human recombinant hematopoietic growth factors. Blood 72: 1682–1686
Ascensao JL, Gaylis F, Bronson D, Fraley EE, Zanjani ED (1983) Erythropoietin production by a human testicular germ cell line. Blood 62: 1132–1134
Baldamus CA, Scigalla P, Wieczorek L, Koch KM (eds) (1989) Erythropoietin: from molecular structure to clinical application. Contrib Nephrol 76: 1–350
Berdel WE, Schick HD, Fink U, Reichert A, Ulm K, Rastetter J (1985) Cytotoxicity of the alkyl-linked lipoidal amine 4-aminomethyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine (CP-46,665) in cells from human tumors and leukemias. Cancer Res 45: 1206–1213
Berdel WE, Danhauser-Riedl S, Steinhauser G, Winton EF (1989) Various human hematopoietic growth factors (Interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of nonhematopoietic tumor cells. Blood 73: 80–83
Berdel WE, Danhauser-Riedl S, Doll M, Herrmann F (1990) Effect of hematopoietic growth factors on the growth of nonhematopoietic tumors cell lines. In: Mertelsmann R, Herrmann F (eds) Hematopoietic growth factors in clinical applications. Marcel Dekker, New York, pp 339–362
Branch DR, Turc J-M, Guilbert LJ (1987) Identification of an erythropoietin-sensitive cell line. Blood 69: 1782–1785
Da Silva J-L, Lacombe C, Bruneval P, Casadevall N, Leporrier M, Camilleri J-P, Bariety J, Tambourin P, Varet B (1990) Tumor cells are the site of erythropoietin synthesis in human renal cancers associated with polycythemia. Blood 75: 577–582
Fraser JK, Lin F-K, Berridge MV (1988) Expression and modulation of specific, high-affinity binding sites for erythropoietin on the human erythroleukemic cell line K562. Blood 71: 104–109
Hagiwara M, Chen I-L, McGonigle R, Beckman B, Kasten FH, Fisher JW (1984) Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice. Blood 63: 828–835
Hagiwara M, Pincus SM, Chen I-L, Beckman B, Fisher JW (1985) Effects of dibutyryl adenosine 3′, 5′-cyclic monophosphate on erythropoietin production in human renal carcinoma cell cultures. Blood 66: 714–717
Hankins WD, Schooley J, Eastment C (1986) Erythropoietin, an autocrine regulator? Serum-free production of erythropoietin by cloned erythroid cell lines. Blood 68: 263–268
Henry D, Keller A, Kugler J, Silver R, Danna R, Staddon A, Mason B, Abels R (1990) Treatment of anemia in cancer patients on cisplatin chemotherapy with recombinant human erythropoietin (rHuEPO). Proc ASCO 9: 182 (abstr. 703)
Ludwig H, Fritz E, Kotzmann H, Höcker P, Gisslinger H, Barnas U (1990) Erythropoietin treatment of anemia associated with multiple myeloma. N Engl J Med 322: 1693–1699
MacDougall IC, Neubert P, Coles GA, Roberts DE, Dharmasena AD, Williams JD (1989) Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Lancet I: 425–427
Maurer HR, Ali-Osman F (1981) Tumor stem cell cloning in agar-containing capillaries. Naturwissenschaften 68: 381–383
Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak LJ (1990) Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 322: 1689–1692
Mitjavila MT, Villeval JL, Cramer P, Henri A, Gasson J, Krystal G, Tulliez M, Berger R, Breton-Gorius J, Vainchenker W (1987) Effects of granulocyte-macrophage colony-stimulating factor and erythropoietin on leukemic erythroid colony formation in human early erythroblastic leukemias. Blood 70: 965–973
Okabe T, Urabe A, Kato T, Chiba S, Takaku F (1985) Production of erythropoietin-like activity by human renal and hepatic carcinomas in cell culture. Cancer 55: 1918–1923
Oster W, Herrmann F, Miller H-G, Brune T, Kraemer H-P, Mertelsmann R (1990) Efficacy of erythropoietin (EPO) to correct anemia due to neoplastic bone marrow infiltration —two routes of administration. Proc AACR 31: 197 (abstr. 1174)
Rudnick S, Abels R, Danna R, Milak D (1990) Correction of chronic anemia in cancer patients by r-HuEPO (EPREX*). Proc ASCO 9: 182 (abstr. 704)
Sherwood JB, Goldwasser E (1976) Erythropoietin production by human renal carcinoma cells in culture. Endocrinology 99: 504–510
Sherwood JB, Burns ER, Shouval D (1987) Stimulation by cAMP of erythropoietin secretion by an established human renal carcinoma cell line. Blood 69: 1053–1057
Todokoro K, Kanazawa S, Amanuma H, Ikawa Y (1987) Specific binding of erythropoietin to its receptor on responsive mouse erythroleukemia cells. Proc Natl Acad Sci USA 84: 4126–4130
Tomonaga M, Jinnai I, Tagawa M, Amenomori T, Nishino K, Yao E, Nonaka H, Kuriyama K, Yoshida Y, Matsuo T, Ichimaru M, Suematsu T (1987) Leukemic blast cell colony formation in semisolid culture with erythropoietin: a case report of acute poorly differentiated erythroid leukemia. Blood 69: 546–552
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This work was supported by a grant from theDeutsche Forschungsgemeinschaft (DFG Be 822/4-2)
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Berdel, W.E., Oberberg, D., Reufi, B. et al. Studies on the role of recombinant human erythropoietin in the growth regulation of human nonhematopoietic tumor cells in vitro. Ann Hematol 63, 5–8 (1991). https://doi.org/10.1007/BF01714953
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DOI: https://doi.org/10.1007/BF01714953