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Expression of von Willebrand factor, an endothelial cell marker, is up‐regulated by angiogenesis factors: A potential method for objective assessment of tumor angiogenesis
Author(s) -
Zanetta Lucia,
Marcus Stuart G.,
Vasile Julie,
Dobryansky Michael,
Cohen Henry,
Eng Kenneth,
Shamamian Peter,
Mignatti Paolo
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000115)85:2<281::aid-ijc21>3.0.co;2-3
Subject(s) - angiogenesis , von willebrand factor , pathology , endothelium , biology , endothelial stem cell , cd31 , vascular endothelial growth factor , cancer research , platelet , immunology , medicine , endocrinology , in vitro , biochemistry , vegf receptors
von Willebrand factor (vWF), a glycoprotein produced uniquely by endothelial cells and megakaryocytes, is routinely used to identify vessels in tissue sections. Vessel density in tumor specimens, as determined by immuno‐histochemical staining for vWF or other endothelial cell markers, is a negative prognostic factor for many solid tumors. vWF is heterogeneously distributed throughout the vasculature, transcriptional control in response to the tissue microenvironment being responsible for local variations in endothelial cell levels of vWF. Here, we report that fibroblast growth factor‐2 and vascular endothelial growth factor, potent angiogenesis inducers expressed in a variety of tumors, up‐regulate expression of vWF mRNA and protein in cultured endothelial cells with a synergistic effect. Our data support the measurement of vWF mRNA in tumors to detect activated endothelium or angiogenesis. For this purpose, we developed a semi‐quantitative RT‐PCR for vWF mRNA. Preliminary results obtained with specimens from colon carcinoma and the corresponding normal colonic mucosa showed higher vWF mRNA levels in most tumors than in their normal counterparts. The differences in vWF mRNA levels were much larger than the differences in vessel counts between a tumor and the corresponding normal mucosa, indicating that high vWF mRNA levels in tumors may indeed be an early sign of activation of the endothelium. The rapidity, objectivity, sensitivity and specificity of this technique make it suitable for routine clinical application to identify aggressive, highly angiogenic tumors. Int. J. Cancer 85:281–288, 2000. ©2000 Wiley‐Liss, Inc.