| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Pathology and Laboratory Medicine,* University of Pennsylvania School of Medicine, and The Wistar Institute, Philadelphia, Pennsylvania
Although erythropoietin (Epo) is a known stimulator of erythropoiesis, recent evidence suggests that its biological functions are not confined to hematopoietic cells. To elucidate the role of Epo and erythropoietin receptor (EpoR) in melanoma, we examined the expression and function of these proteins in melanocytes and melanoma cells. We found increased expression of Epo in melanoma cells compared to melanocyte in vitro. EpoR was also strongly expressed in all of the melanoma cell lines and two of the three melanocyte cell lines examined. Epo expression was significantly higher in melanoma than in benign nevi as determined by immunohistochemistry. Although melanoma cells secreted Epo in normoxic condition in vitro, hypoxia and CoCl2 treatment increased Epo secretion. EpoR in melanoma cells was functional, because exogenous Epo increased melanoma resistance to hypoxic stress, pretreatment of melanoma cells with Epo significantly increased resistance to dacarbazine treatment, and Epo increased the phosphorylation of EpoR, RAF, and MEK. In conclusion, we demonstrated constitutive expression of Epo and EpoR as well as autonomous secretion of Epo by melanoma cells, indicating a novel autocrine loop of Epo in melanoma. The results suggest that the autocrine and paracrine functions of Epo might play a role in malignant transformation of melanocytes and in the survival of melanoma cells in hypoxia and other adverse conditions.
This article has been cited by other articles:
 |
|
 |
|
  M. O. Arcasoy Erythropoiesis-Stimulating Agent Use in Cancer: Preclinical and Clinical Perspectives Clin. Cancer Res., August 1, 2008; 14(15): 4685 - 4690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. May and F. R. Khuri Unraveling the Mystery of Erythropoietin-Stimulating Agents in Cancer Promotion Cancer Res., June 1, 2008; 68(11): 4013 - 4017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Saintigny, B. Besse, J.-C. Soria, J.-F. Bernaudin, and P. Callard Does Erythropoietin Promote Tumor Growth? Clin. Cancer Res., March 15, 2008; 14(6): 1920 - 1921. [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Bennett, S. M. Silver, B. Djulbegovic, A. T. Samaras, C. A. Blau, K. J. Gleason, S. E. Barnato, K. M. Elverman, D. M. Courtney, J. M. McKoy, et al. Venous Thromboembolism and Mortality Associated With Recombinant Erythropoietin and Darbepoetin Administration for the Treatment of Cancer-Associated Anemia JAMA, February 27, 2008; 299(8): 914 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bodo, A. Kromminga, W. Funk, M. Laugsch, U. Duske, W. Jelkmann, and R. Paus Human hair follicles are an extrarenal source and a nonhematopoietic target of erythropoietin FASEB J, October 1, 2007; 21(12): 3346 - 3354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Saintigny, B. Besse, P. Callard, A.-C. Vergnaud, S. Czernichow, M. Colombat, P. Girard, P. Validire, J.-L. Breau, J.-F. Bernaudin, et al. Erythropoietin and Erythropoietin Receptor Coexpression Is Associated with Poor Survival in Stage I Non Small Cell Lung Cancer Clin. Cancer Res., August 15, 2007; 13(16): 4825 - 4831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kokhaei, A. O. Abdalla, L. Hansson, E. Mikaelsson, M. Kubbies, A. Haselbeck, H. Jernberg-Wiklund, H. Mellstedt, and A. Osterborg Expression of Erythropoietin Receptor and In vitro Functional Effects of Epoetins in B-Cell Malignancies Clin. Cancer Res., June 15, 2007; 13(12): 3536 - 3544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kumar, H. Yu, R. Edwards, L. Chen, S. Kazianis, P. Brafford, G. Acs, M. Herlyn, and X. Xu Mutant V600E BRAF Increases Hypoxia Inducible Factor-1{alpha} Expression in Melanoma Cancer Res., April 1, 2007; 67(7): 3177 - 3184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Menon, J. Fang, and D. M. Wojchowski Core erythropoietin receptor signals for late erythroblast development Blood, April 1, 2006; 107(7): 2662 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. LaMontagne, J. Butler, D. J. Marshall, J. Tullai, Z. Gechtman, C. Hall, A. Meshaw, and F. X. Farrell Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor-positive breast carcinoma models. Mol. Cancer Ther., February 1, 2006; 5(2): 347 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Hardee, M. O. Arcasoy, K. L. Blackwell, J. P. Kirkpatrick, and M. W. Dewhirst Erythropoietin Biology in Cancer Clin. Cancer Res., January 15, 2006; 12(2): 332 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Winter, K. A. Shah, L. Campo, H. Turley, R. Leek, R. J. Corbridge, G. J. Cox, and A. L. Harris Relation of Erythropoietin and Erythropoietin Receptor Expression to Hypoxia and Anemia in Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., November 1, 2005; 11(21): 7614 - 7620. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
