Carcinogenesis Advance Access published online on April 24, 2003
Carcinogenesis, doi:10.1093/carcin/bgg060
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARCINOGENESIS
1 Department of Anatomy, Division 1 Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511
* Corresponding author. E-mail: y1126yas{at}med.kindai.ac.jp.
Received 30 October 2002
; revised 31 January 2003
; accepted 4 April 2003
In addition to the chief function of erythropoietin in promoting erythropoiesis, some other roles have been found in the brain and uterus. We have reported that signalling pathways of erythropoietin and erythropoietin receptor are involved in the tumourigenesis of ovarian and uterine cancers. To determine whether erythropoietin plays a similar role in other malignancies, we planned a study of the expression of erythropoietin in several malignant human cell lines. We found that 24 malignant human cell lines examined express erythropoietin and erythropoietin receptor mRNA regardless of their origins, types, genetic characteristics and biological properties and secrete a very small amount of erythropoietin individually and that most of them respond to hypoxic stimuli by enhanced secretion of erythropoietin. To determine whether erythropoietin-erythropoietin receptor pathway operates in tumours of these cell lines, we transplanted several cell lines into nude mice and confirmed the presence of erythropoietin responsive sites in xenografts in which the phosphorylation of the STAT5 is detectable. Furthermore, in nude mice we blocked the erythropoietin signalling in xenografts of two representative cell lines, stomach choriocarcinoma and melanoma, by intraperitoneal injections of erythropoietin receptor antagonist and found inhibition of angiogenesis and survival of tumour cells leading to destruction of tumour masses and disturbances of phosphorylation of STAT5. In contrast, erythropoietin mimetic peptide promotes angiogenesis and tumour cell survival. These findings suggest that erythropoietin is indispensable for the growth and viability of malignant tumour and also that the deprivation of erythropoietin signalling may be a promising therapy for human malignancy.
Erythropoietin regulates tumour growth of human malignancies
2 Department of Surgery, Division 1 Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511
3 Research Reactor Institute of Kyoto University, Osaka 590-0451
4 Department of Obstetrics and Gynaecology, Kyorin University School of Medicine, Mitaka 181-8611
5 Laboratory of Environmental Biology, Hokkaido University School of Medicine, Hokkaido 060-8638, Japan
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. K. Hadland and G. D. Longmore Erythroid-Stimulating Agents in Cancer Therapy: Potential Dangers and Biologic Mechanisms J. Clin. Oncol., September 1, 2009; 27(25): 4217 - 4226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-M. Larsson, K. Jirstrom, E. Fredlund, S. Nilsson, L. Ryden, G. Landberg, and S. Pahlman Erythropoietin Receptor Expression and Correlation to Tamoxifen Response and Prognosis in Breast Cancer Clin. Cancer Res., September 1, 2009; 15(17): 5552 - 5559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Jeong, G. Hoxhaj, A. L. Socha, A. J. Sytkowski, and L. Feldman An Erythropoietin Autocrine/Paracrine Axis Modulates the Growth and Survival of Human Prostate Cancer Cells Mol. Cancer Res., July 1, 2009; 7(7): 1150 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 C. Bose and K. B. Udupa Erythropoietin enhancement of rat pancreatic tumor cell proliferation requires the activation of ERK and JNK signals Am J Physiol Cell Physiol, August 1, 2008; 295(2): C394 - C405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Chabowska, M. Sulkowska, A. Chabowski, A. Wincewicz, M. Koda, and S. Sulkowski Erythropoietin and Erythropoietin Receptor in Colorectal Cancer International Journal of Surgical Pathology, July 1, 2008; 16(3): 269 - 276. [Abstract] [PDF]
|
|
|
|
 |
|
 J. P. Pinto, S. Ribeiro, H. Pontes, S. Thowfeequ, D. Tosh, F. Carvalho, and G. Porto Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBP{alpha} Blood, June 15, 2008; 111(12): 5727 - 5733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pirker, R. A. Ramlau, W. Schuette, P. Zatloukal, I. Ferreira, T. Lillie, and J. F. Vansteenkiste Safety and Efficacy of Darbepoetin Alfa in Previously Untreated Extensive-Stage Small-Cell Lung Cancer Treated With Platinum Plus Etoposide J. Clin. Oncol., May 10, 2008; 26(14): 2342 - 2349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Hamadmad and R. J. Hohl Erythropoietin Stimulates Cancer Cell Migration and Activates RhoA Protein through a Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase-Dependent Mechanism J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1227 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Shankar The Role of Recombinant Erythropoietin in Childhood Cancer Oncologist, February 1, 2008; 13(2): 157 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Pelekanou, M. Kampa, M. Kafousi, K. Dambaki, K. Darivianaki, T. Vrekoussis, E. Sanidas, D. D. Tsiftsis, E. N. Stathopoulos, and E. Castanas Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2016 - 2023. [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]
|
|
|
|
 |
|
 A. J. Sytkowski Does Erythropoietin Have a Dark Side? Epo Signaling and Cancer Cells Sci. Signal., July 17, 2007; 2007(395): pe38 - pe38. [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]
|
|
|
|
 |
|
 F Bellati, M Pernice, N Manci, I Palaia, F Tomao, C Marchetti, M. Zullo, L Muzii, R Angioli, and P. B. Panici Hemoglobin variation and blood transfusion rates in patients affected by locally advanced cervical cancer undergoing neo-adjuvant chemotherapy followed by radical surgery: the role of erythropoietic growth factors Ann. Onc., April 1, 2007; 18(4): 722 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Leo, L.-C. Horn, C. Rauscher, B. Hentschel, A. Liebmann, G. Hildebrandt, and M. Hockel Expression of Erythropoietin and Erythropoietin Receptor in Cervical Cancer and Relationship to Survival, Hypoxia, and Apoptosis Clin. Cancer Res., December 1, 2006; 12(23): 6894 - 6900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Lai and J. R. Grandis Understanding the Presence and Function of Erythropoietin Receptors on Cancer Cells J. Clin. Oncol., October 10, 2006; 24(29): 4675 - 4676. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bohlius, J. Wilson, J. Seidenfeld, M. Piper, G. Schwarzer, J. Sandercock, S. Trelle, O. Weingart, S. Bayliss, B. Djulbegovic, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst, May 17, 2006; 98(10): 708 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Gewirtz, X. Di, T. D. Walker, and S. T. Sawyer Erythropoietin fails to interfere with the antiproliferative and cytotoxic effects of antitumor drugs. Clin. Cancer Res., April 1, 2006; 12(7): 2232 - 2238. [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]
|
|
|
|
 |
|
 R. D. Lester, M. Jo, W. M. Campana, and S. L. Gonias Erythropoietin Promotes MCF-7 Breast Cancer Cell Migration by an ERK/Mitogen-activated Protein Kinase-dependent Pathway and Is Primarily Responsible for the Increase in Migration Observed in Hypoxia J. Biol. Chem., November 25, 2005; 280(47): 39273 - 39277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sfacteria, G. Mazzullo, C. Bertani, P. Calabro, G. De Vico, and B. Macri Erythropoietin Receptor Expression in Canine Mammary Tumor: An Immunohistochemical Study Vet. Pathol., November 1, 2005; 42(6): 837 - 840. [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]
|
|
|
|
|
|
A. Engert Recombinant human erythropoietin in oncology: current status and further developments Ann. Onc., October 1, 2005; 16(10): 1584 - 1595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Steensma and C. L. Loprinzi Erythropoietin Use in Cancer Patients: A Matter of Life and Death? J. Clin. Oncol., September 1, 2005; 23(25): 5865 - 5868. [Full Text] [PDF]
|
|
|
|
|
|
R. Stasi, S. Amadori, T. J. Littlewood, E. Terzoli, A. C. Newland, and D. Provan Management of Cancer-Related Anemia with Erythropoietic Agents: Doubts, Certainties, and Concerns Oncologist, August 1, 2005; 10(7): 539 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. A. Vogel, F. M. Brouwers, I. A. Lubensky, A. O. Vortmeyer, R. J. Weil, M. M. Walther, E. H. Oldfield, W. M. Linehan, K. Pacak, and Z. Zhuang Differential Expression of Erythropoietin and Its Receptor in von Hippel-Lindau-Associated and Multiple Endocrine Neoplasia Type 2-Associated Pheochromocytomas J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3747 - 3751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bohlius, S. Langensiepen, G. Schwarzer, J. Seidenfeld, M. Piper, C. Bennett, and A. Engert Recombinant Human Erythropoietin and Overall Survival in Cancer Patients: Results of a Comprehensive Meta-analysis J Natl Cancer Inst, April 6, 2005; 97(7): 489 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Weiss and L. T. Goodnough Anemia of Chronic Disease N. Engl. J. Med., March 10, 2005; 352(10): 1011 - 1023. [Full Text] [PDF]
|
|
|
|
|
|
K. Dagnon, E. Pacary, F. Commo, M. Antoine, M. Bernaudin, J.-F. Bernaudin, and P. Callard Expression of Erythropoietin and Erythropoietin Receptor in Non-Small Cell Lung Carcinomas Clin. Cancer Res., February 1, 2005; 11(3): 993 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Arcasoy, K. Amin, S.-C. Chou, Z. A. Haroon, M. Varia, and J. A. Raleigh Erythropoietin and Erythropoietin Receptor Expression in Head and Neck Cancer: Relationship to Tumor Hypoxia Clin. Cancer Res., January 1, 2005; 11(1): 20 - 27. [Abstract] [Full Text] [PDF]
|
|