| First Author | Kim JW | Year | 2012 |
| Journal | Cancer Res | Volume | 72 |
| Issue | 13 | Pages | 3187-95 |
| PubMed ID | 22556263 | Mgi Jnum | J:189318 |
| Mgi Id | MGI:5445045 | Doi | 10.1158/0008-5472.CAN-12-0534 |
| Citation | Kim JW, et al. (2012) Loss of fibroblast HIF-1alpha accelerates tumorigenesis. Cancer Res 72(13):3187-95 |
| abstractText | Solid tumors consist of malignant cells and associated stromal components, including fibroblastic cells that contribute to tumor growth and progression. Although tumor fibrosis and aberrant vascularization contribute to the hypoxia often found in advanced tumors, the contribution of hypoxic signaling within tumor-associated fibroblasts to tumorigenesis remains unknown. In this study, we used a fibroblast-specific promoter to create mice in which key hypoxia regulatory genes, including VHL, HIF-1alpha, HIF-2alpha, and VEGF-A, were knocked out specifically in tumor stromal fibroblasts. We found that loss of HIF-1alpha and its target gene VEGF-A accelerated tumor growth in murine model of mammary cancer. HIF-1alpha and VEGF-A loss also led to a reduction in vascular density and myeloid cell infiltration, which correlated with improved tumor perfusion. Together, our findings indicate that the fibroblast HIF-1alpha response is a critical component of tumor vascularization. |
