Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis
| Autor: | Boaz Pal, Shafika Kasem, Katia Beider, Rinat Abramovitch, Evelyne Zeira, Rebekah Karplus, Eithan Galun, Eli Pikarsky, Merav Darash-Yahana, Amnon Peled, Shani Avniel |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Receptors CXCR4 Lung Neoplasms Recombinant Fusion Proteins Transplantation Heterologous Bone Neoplasms Breast Neoplasms Mice SCID Adenocarcinoma Biochemistry CXCR4 Metastasis Mice Chemokine receptor Prostate cancer Breast cancer Bone Marrow Cell Movement Mice Inbred NOD Prostate Cell Line Tumor Cell Adhesion Genetics medicine Animals Humans Neoplasm Metastasis Molecular Biology Lymph node Ovarian Neoplasms Hyperplasia Neovascularization Pathologic business.industry Prostatic Neoplasms medicine.disease Magnetic Resonance Imaging Chemokine CXCL12 Neoplasm Proteins Phenotype medicine.anatomical_structure Organ Specificity Lymphatic Metastasis Cancer research Female business Chemokines CXC Biotechnology |
| Zdroj: | The FASEB Journal. 18:1240-1242 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.03-0935fje |
| Popis: | Hormone refractory metastatic prostate cancer remains an incurable disease. We found that high expression levels of the chemokine receptor CXCR4 correlated with the presence of metastatic disease in prostate cancer patients. Positive staining for CXCL12, the ligand for CXCR4, was mainly present in the tumor-associated blood vessels and basal cell hyperplasia. Subcutaneous xenografts of PC3 and 22Rv1 prostate tumors that overexpressed CXCR4 in NOD/SCID mice were two- to threefold larger in volume and weight vs. controls. Moreover, blood vessel density, functionality, invasiveness of tumors into the surrounding tissues, and metastasis to the lymph node and lung were significantly increased in these tumors. Neutralizing the interactions of CXCL12/CXCR4 in vivo with CXCR4 specific antibodies inhibited the CXCR4-dependent tumor growth and vascularization. In vitro, CXCL12 induced the proliferation and VEGF secretion but not migration of PC3 and 22Rv1 cells overexpressing CXCR4. Similar effects of CXCR4 overexpression on tumor growth in vivo were also noted in two breast cancer lines, suggesting that the observed effect of CXCR4 is not unique to prostate tumor cells. Thus high levels of the chemokine receptor CXCR4 induce a more aggressive phenotype in prostate cancer cells and identify CXCR4 as a potential therapeutic target in advanced cases of metastatic prostate cancer. |
| Databáze: | OpenAIRE |
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