Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade Journal Article
| Authors: | Li, H.; Gerald, W. L.; Benezra, R. |
| Article Title: | Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade |
| Abstract: | Id1 and Id3 genes are required for vascularization, growth, and metastasis of xenograft tumors. In Id-deficient mice, tumor transplantation and proangiogenic factors fail to mobilize and recruit circulating endothelial precursor cells (CEPs) and hematopoietic cells, leading to defective tumor angiogenesis in various models. To investigate the requirement of Id genes and bone marrow incorporation in spontaneous prostate tumors, we crossbred Id mutant mice with the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Id1-/- Id3+/- TRAMP mice display delayed tumor growth at 24 weeks compared with wild-type TRAMP mice. Id1 and Id3 were strongly expressed in the endothelial cells of poorly differentiated prostate adenocarcinoma but not in the vasculature of well-differentiated tumors, a finding that is corroborated in human prostate tumor samples. In Id-deficient TRAMP mice, the poorly differentiated tumors show extensive hemorrhage, whereas well-differentiated tumors exhibit none. Transplantation with Id wild-type bone marrow significantly reduced the hemorrhage in poorly differentiated prostate adenocarcinomas with bone marrow-derived endothelial cells contributing to 14% of the tumor blood vessels. However, in well-differentiated prostate adenocarcinomas, there was little evidence of bone marrow-derived endothelial cell incorporation. These differences in the expression of Id genes, the effects of Id loss, and the recruitment of bone marrow-derived endothelial precursor cells in tumor vasculature between well-differentiated and poorly differentiated prostate adenocarcinoma suggest that tumor angiogenesis varies depending on the tumor grade. |
| Keywords: | immunohistochemistry; controlled study; human tissue; human cell; dna-binding proteins; nonhuman; cancer grading; adenocarcinoma; animal cell; mouse; mouse mutant; animals; mice; animal tissue; gene; bone marrow cells; gene expression; bone marrow; animal experiment; animal model; cell differentiation; angiogenesis; neovascularization, pathologic; mice, inbred c57bl; transgenic mouse; transcription factors; stem cell; prostatic neoplasms; endothelium cell; in situ hybridization; xenograft; endothelium, vascular; prostate tumor; hematopoietic cell; prostate adenocarcinoma; bone marrow cell; inhibitor of differentiation protein 1; mouse strain; bone marrow transplantation; repressor proteins; tumor bleeding; angiogenic factor; cancer transplantation; receptors, tumor necrosis factor; tumor angiogenesis; tumor blood flow; id gene; inhibitor of differentiation protein 2; human; male; priority journal; article; receptors, tumor necrosis factor, member 25; bone marrow derived endothelial cell; id1 gene; id3 gene; transgenic adenocarcinoma of the mouse prostate; tumor blood vessel |
| Journal Title: | Cancer Research |
| Volume: | 64 |
| Issue: | 17 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-09-01 |
| Start Page: | 6137 |
| End Page: | 6143 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-04-1287 |
| PROVIDER: | scopus |
| PUBMED: | 15342397 |
| DOI/URL: | |
| Notes: | Cancer Res. -- Cited By (since 1996):63 -- Export Date: 16 June 2014 -- CODEN: CNREA -- Source: Scopus |
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