Hlatky L, Tsionou C, Hahnfeldt P, Coleman C N
Department of Radiation Oncology, Harvard Medical School, Boston, Massachusetts 02115.
Cancer Res. 1994 Dec 1;54(23):6083-6.
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.
最近的研究表明了微血管密度与乳腺癌恶性进展之间的关系（N. 魏德纳、J. P. 森普尔、W. R. 韦尔奇和J. 福克曼，《新英格兰医学杂志》，324: 1 - 8, 1991），强调了血管生成在这种肿瘤中的重要性。肿瘤分泌因子（如血管内皮生长因子）的旁分泌作用在肿瘤血管生成中至关重要，这些因子一直被认为来源于肿瘤上皮细胞本身。我们证明，在低氧条件下，人乳腺成纤维细胞会显著上调血管内皮生长因子mRNA，并根据缺氧程度增加血管内皮生长因子蛋白水平。因此，乳腺基质细胞，直到最近才被认为参与乳腺癌的调控，可能在乳腺癌血管生成中发挥迄今未被认识到的作用。
