| First Author | Jodele S | Year | 2005 |
| Journal | Cancer Res | Volume | 65 |
| Issue | 8 | Pages | 3200-8 |
| PubMed ID | 15833851 | Mgi Jnum | J:97827 |
| Mgi Id | MGI:3576452 | Doi | 10.1158/0008-5472.CAN-04-3770 |
| Citation | Jodele S, et al. (2005) The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. Cancer Res 65(8):3200-8 |
| abstractText | The contribution of the tumor stroma to cancer progression has been increasingly recognized. We had previously shown that in human neuroblastoma tumors orthotopically implanted in immunodeficient mice, stromal-derived matrix metalloproteinase-9 (MMP-9) contributes to the formation of a mature vasculature by promoting pericyte recruitment along endothelial cells. Here we show that MMP-9 is predominantly expressed by bone marrow-derived CD45-positive leukocytes. Using a series of bone marrow transplantation experiments in MMP-9(+/+) and MMP-9(-/-) mice xenotransplanted with human neuroblastoma tumors, we show that bone marrow-derived MMP-9 is critical for the recruitment of leukocytes from bone marrow into the tumor stroma and for the integration of bone marrow-derived endothelial cells into the tumor vasculature. Expression of MMP-9 by bone marrow-derived cells in the tumor stroma is also critical for the formation of a mature vasculature and coverage of endothelial cells with pericytes. Furthermore, in primary human neuroblastoma tumor specimens of unfavorable histology, we observed a higher level of tumor infiltration with MMP-9 expressing phagocytic cells and a higher degree of coverage of endothelial cells by pericytes when compared with tumor specimens with a favorable histology. Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow-derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression. |
