Mammary fibroblasts may influence breast tumor angiogenesis via hypoxia-induced vascular endothelial growth factor up-regulation and protein expression

L Hlatky, C Tsionou, P Hahnfeldt, CN Coleman - Cancer research, 1994 - AACR
L Hlatky, C Tsionou, P Hahnfeldt, CN Coleman
Cancer research, 1994AACR
Recent studies demonstrate the relationship of microvessel density to malignant progression
in breast cancer (N. Weidner, JP Semple, WR Welch, and J. Folkman, N. Engl. J. Med., 324:
1–8, 1991), underscoring the importance of angiogenesis in this tumor. Crucial in tumor
angiogenesis are the paracrine actions of tumor-secreted factors (eg, vascular endothelial
growth factor), which have been thought to derive from the tumor epithelial cells themselves.
We demonstrate that in response to hypoxic conditions, human mammary fibroblasts …
Abstract
Recent studies demonstrate the relationship of microvessel density to malignant progression in breast cancer (N. Weidner, J. P. Semple, W. R. Welch, and J. Folkman, N. Engl. J. Med., 324: 1–8, 1991), underscoring the importance of angiogenesis in this tumor. Crucial in tumor angiogenesis are the paracrine actions of tumor-secreted factors (e.g., vascular endothelial growth factor), which have been thought to derive from the tumor epithelial cells themselves. We demonstrate that in response to hypoxic conditions, human mammary fibroblasts dramatically up-regulate vascular endothelial growth factor mRNA and increase vascular endothelial growth factor protein levels in accordance with the degree of oxygen deprivation. Thus, mammary stromal cells, only recently considered in the regulation of breast carcinomas, may play a hitherto unrealized role in breast cancer angiogenesis.
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