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Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model

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Abstract

Background

Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.

Methods

Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1–11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.

Results

Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.

Conclusion

Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

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References

  1. Beck SA, Tisdale MJ (1987) Production of lipolytic and proteolytic factors by a murine tumor producing cachexia in the host. Cancer Res 47:5919–5923

    CAS  PubMed  Google Scholar 

  2. Tisdale MJ, Beck SA (1991) Inhibition of tumor-induced lipolysis in vitro and cachexia and tumor growth in vivo by eicosapentanoic acid. Biochem Pharmacol 41:103–107

    Article  CAS  PubMed  Google Scholar 

  3. Groundwater P, Beck SA, Barton C, Adamson C, Ferrier IN, Tisdale MJ (1990) Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients. Br J Cancer 62:816–821

    CAS  PubMed  Google Scholar 

  4. Beck SA, Mullingan HD, Tisdale MJ (1990) Lipolytic factors associated with murine and human cancer cachexia. J Natl Cancer Inst 82:1922–1926

    CAS  PubMed  Google Scholar 

  5. Todorov PT, McDevitt TM, Cariuk P, Coles B, Deacon M, Tisdale MJ (1996) Induction of muscle protein degradation and weight loss by a tumor product. Cancer Res 56:1256–1261

    CAS  PubMed  Google Scholar 

  6. Cabal-Manzano R, Bhargava P, Torres-Duarte A, Marshall J, Bhargava P, Wainer IW (2001) Proteolysis-inducing factor is expressed in tumors of patients with gastrointestinal cancers and correlates with weight loss. Br J Cancer 84:1599–1601

    Google Scholar 

  7. Lorite MJ, Cariuk P, Tisdale M (1997) Induction of muscle protein degradation by a tumor factor. Br J Cancer 76:1035–1040

    CAS  PubMed  Google Scholar 

  8. Wigmore SJ, Ross JA, Falconer JS, Plester CE, Tisdale MJ, Carter DC, et al (1996) The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition 12[Suppl 1]:27–30

  9. Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KCH (1999) The effect of an oral nutritional supplement inriched with fish oil on weight loss in patients with pancreatic cancer. Br J Cancer 81:80–86

    CAS  PubMed  Google Scholar 

  10. Holm E, Hagmüller E, Staedt U (1995) Substrate balances across colonic carcinomas in humans. Cancer Res 55:1373–1378

    CAS  PubMed  Google Scholar 

  11. Holroyde C, Gabuzda TG, Putnam RC, Paul P, Reichard GA (1975) Altered glucose metabolism in metastatic carcinoma. Cancer Res 35:3710–3714

    CAS  PubMed  Google Scholar 

  12. Holroyde CP, Axelrod RS, Skutches CL, Haff AC, Paul P, Reichard GA (1979) Lactate metabolism in patients with metastatic colorectal cancer. Cancer Res 39:4900–4904

    CAS  PubMed  Google Scholar 

  13. Holroyde CP, Skutches CL, Boden G, Reichard GA (1984) Glucose metabolism in cachectic patients with colorectal cancer. Cancer Res :44:5910–5913

    Google Scholar 

  14. Roeder I, de Haan G, Nijhof W, Dontje B, Loeffler M (1998) Interactions of erythropoietin, granulocyte colony-stimulating factor, stem cell factor and interleukin-11 on murine hematopoiesis during simultaneous administration. Blood 91:3222–3229

    CAS  PubMed  Google Scholar 

  15. Teicher BA, Holden SA, Menon K, Hopkins RE, Gawril MS (1993) Effect of hemoglobin solution on the response of intracranial and subcutaneous 9L tumors to antitumor alkylating agents. Cancer Chemother Pharmacol 33:57–62

    CAS  PubMed  Google Scholar 

  16. Teicher BA, Schwartz GN, Alvarez Sotomayor E, Robinson MF, Dupuis NP, Menon K (1993) Oxygenation of tumors by hemoglobin solution. J Cancer Res Clin Oncol 120:85–90

    CAS  PubMed  Google Scholar 

  17. Teicher BA, Holden SA, Dupuis NP, Kusomoto T, Liu M, Liu F, et al (1994) Oxygenation of the rat gliosarcoma and the rat 13672 mammary carcinoma with various doses of a hemoglobin solution. Artif Cells Blood Substit Immobil Biotechnol 22:827–833

    CAS  PubMed  Google Scholar 

  18. Kelleher DK, Matthiensen U, Thews O, Vaupel P (1996) Blood flow, oxygenation and bioenergetic status of tumors after erythropoietin treatment in normal and anemic rats. Cancer Res 56:4728–4732

    CAS  PubMed  Google Scholar 

  19. Becker A, Stadler P, Lavey RS, Hänsgen G, Kuhnt T, Lautenschläger C, et al (2000) Severe anemia is associated with poor tumor oxygenation in head and neck squamous cell carcinomas. Int J Radiation Oncology Biol Phys 46:459–466

    Article  CAS  Google Scholar 

  20. Vaupel P, Thews O, Mayer A, Hockel S, Hockel M (2002) Oxygenation status of gynecologic tumors:what is the optimal hemoglobin level? Strahlenther Onkol 178:727–731

    Article  PubMed  Google Scholar 

  21. Acs G, Acs P, Beckwith SM, Pitts RL, Clements E, Wong K, et al (2001) Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Res 61:3561–3565

    CAS  PubMed  Google Scholar 

  22. Acs G, Zhang PJ, Rebbeck TR, Acs P, Verma A (2002) Immunohistochemical expression of erythropoietin and erythropoietin receptor in breast carcinoma. Cancer 95:969–981

    Article  CAS  PubMed  Google Scholar 

  23. Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C, et al (2000) Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 97:10526–10531

    Article  CAS  PubMed  Google Scholar 

  24. Dunphy FR, Harrison BR, Dunleavy TL, Rodriguez JJ, Hilton JG, Boyd JH (1999) Erythropoietin reduces anemia and transfusions. Cancer 86:2362–2367

    Article  Google Scholar 

  25. Demetri GD, Kris M, Wade J, Degos L, Cella D (1998) Quality-of-life benefit in chemotherapy patients treated with epoetin alfa is independent of disease response or tumor type:results from a prospective community oncology study. J Clin Oncol 16:3412–3425

    CAS  PubMed  Google Scholar 

  26. Glaspy J, Bukowski R, Steinberg D, Taylor C, Tcheckmedyian S, Vadhan-Raj S (1997) Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice. J Clin Oncol 15:1218–1234

    CAS  PubMed  Google Scholar 

  27. Klaesson S, Ringdén O, Ljungman P, Lönnquist B, Wennberg L (1994) Reduced blood transfusion requirements after allogeneic bone marrow transplantation: results of a randomized, double-blind study with high-dose erythropoietin. Bone Marrow Transplant 13:397–402

    CAS  PubMed  Google Scholar 

  28. Daneryd P, Svanberg E, Körner U, Lindholm E, Sandström R, Brevinge H, et al (1998) Protection of metabolic and exercise capacity in unselected weight-losing cancer patients following treatment with recombinant erythropoietin: a randomized prospective study. Cancer Res 58:5374–5379

    CAS  PubMed  Google Scholar 

  29. Csáki C, Ferencz T, Schuler D, Borsi JD (1998) Recombinant human erythropoietin in the prevention of chemotherapy-induced anemia in children with malignant solid tumors. Eur J Cancer 34:364–367

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Oosterschelde Hospital, PO Box 106, 4460 BB , Goes, The Netherlands

    H. K. van Halteren

  2. Department of Medical Oncology, University Medical Center, Nijmegen, The Netherlands

    H. K. van Halteren, C. A. M. Verhagen, Y. J. L. Kamm & D. J. Th. Wagener

  3. Department of Medical Microbiology, University Medical Center, Nijmegen, The Netherlands

    G. P. A. Bongaerts

  4. Department of Clinical Chemistry, University Medical Center, Nijmegen, The Netherlands

    J. L. Willems

  5. Central Animal Laboratory, University of Nijmegen, The Netherlands

    G. J. Grutters & J. P. Koopman

Authors
  1. H. K. van Halteren
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  2. G. P. A. Bongaerts
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  3. C. A. M. Verhagen
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  4. Y. J. L. Kamm
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  5. J. L. Willems
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  6. G. J. Grutters
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  7. J. P. Koopman
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  8. D. J. Th. Wagener
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Corresponding author

Correspondence to H. K. van Halteren.

Additional information

This study was financially supported by a grant from Ortho Biotech, a division of Janssen Cilag, Tilburg, the Netherlands

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van Halteren, H.K., Bongaerts, G.P.A., Verhagen, C.A.M. et al. Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model. J Cancer Res Clin Oncol 130, 211–216 (2004). https://doi.org/10.1007/s00432-003-0526-7

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  • DOI: https://doi.org/10.1007/s00432-003-0526-7

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