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

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 par...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-12, Vol.54 (23), p.6083-6086
Main Authors: HLATKY, L, TSIONOU, C, HAHNFELDT, P, COLEMAN, C. N
Format: Article
Language:English
Subjects:
Biological and medical sciences
Breast - cytology
Breast - metabolism
Breast Neoplasms - blood supply
Cell Hypoxia
Cells, Cultured
Endothelial Growth Factors - biosynthesis
Endothelial Growth Factors - genetics
Female
Fibroblasts - physiology
Gynecology. Andrology. Obstetrics
Humans
Lymphokines - biosynthesis
Lymphokines - genetics
Mammary gland diseases
Medical sciences
Neovascularization, Pathologic
RNA, Messenger - analysis
Tumors
Up-Regulation
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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Summary: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.
ISSN:0008-5472
1538-7445