Pediatric Tumor Cells Express Erythropoietin and a Functional Erythropoietin Receptor that Promotes Angiogenesis and Tumor Cell Survival
| Autor: | Natalya Perelman, Sandeep Batra, Hiroyuki Shimada, Lori R Luck, Punam Malik |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cell Survival Angiogenesis Endothelial Growth Factors Pregnancy Proteins Biology Pathology and Forensic Medicine chemistry.chemical_compound hemic and lymphatic diseases Receptors Erythropoietin Tumor Cells Cultured medicine Humans RNA Messenger RNA Neoplasm Fluorescent Antibody Technique Indirect Erythropoietin Molecular Biology Placenta Growth Factor Medulloblastoma Lymphokines Dose-Response Relationship Drug Neovascularization Pathologic Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factors Infant Cancer Cell Biology Neoplasms Germ Cell and Embryonal medicine.disease Cell Hypoxia Erythropoietin receptor Gene Expression Regulation Neoplastic Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Child Preschool Cancer research Intercellular Signaling Peptides and Proteins Sarcoma medicine.drug |
| Zdroj: | Laboratory Investigation. 83:1477-1487 |
| ISSN: | 0023-6837 |
| DOI: | 10.1097/01.lab.0000090156.94795.48 |
| Popis: | Erythropoietin was traditionally considered an erythroid-restricted cytokine, but recent evidence indicates a broader role for it in nonhematopoietic tissues, specifically in neural development. Pediatric solid tumors are mostly developmental in origin, and more than 50% of the solid tumors are neural in origin. We found erythropoietin receptor and erythropoietin expression in common pediatric tumor cells: neuroblastomas, Ewing's sarcoma family of tumors, pediatric brain tumors (medulloblastoma, astrocytoma, and ependymoma), Wilms tumors, rhabdomyosarcomas, and hepatoblastomas (n = 24), and in cell lines derived from some of these tumors (n = 25). Expression of erythropoietin in tumor cell lines was hypoxia-inducible. Addition of exogenous erythropoietin to tumor cell lines expressing erythropoietin receptor increased nuclear DNA binding activity of nuclear factor kappa B and increased the expression of the antiapoptotic genes bcl-1, bcl-xL, and mcl-1. Additionally, exogenous erythropoietin increased production and secretion of angiogenic growth factors, vascular endothelial growth factor, or placenta growth factor from the tumor cell lines, which promoted endothelial cell proliferation and chemotaxis. Erythropoietin receptor expression that promotes tumor cell survival and releases angiogenic growth factors in pediatric tumors has not been previously described. Therefore, a careful evaluation of the impact of erythropoietin is warranted in vivo, in xenograft models of pediatric tumors, followed by evaluation in pediatric patients with cancer. |
| Databáze: | OpenAIRE |
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