Tumor specific activation of the VEGF/KDR angiogenic pathway in a subset of locally advanced squamous cell head and neck carcinomas |
| |
Authors: | Alexandra Giatromanolaki Michael I Koukourakis Efthimios Sivridis Philip E Thorpe Rolf A Brekken Simopoulos Konstantinos George Fountzilas Kevin C Gatter Adrian L Harris |
| |
Institution: | (1) Departments of Pathology, of Surgery and of Radiotherapy/Oncology, Democritus University of Thrace, P.O. Box 128, Alexandroupolis, Greece;(2) Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA;(3) Department of Medical Oncology, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;(4) Departments of Cellular Science and ICRF Medical Oncology Unit, Oxford Radcliffe Hospital Headington, Oxford, UK |
| |
Abstract: | Vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and flk-1(KDR), constitute an important angiogenic pathway
which, under hypoxic conditions, is up-regulated in many solid tumours. We used the monoclonal antibody 11B5, specific for
recognizing VEGF expression and the `VEGF/flk-1(KDR) complex' on tumour endothelium, to assess free VEGF protein expression
and VEGF/receptor activated microvessel density (aMVD) in a series of 104 inoperable locally advanced squamous cell carcinomas
of the head and neck, treated with chemo-radiotherapy. High VEGF expression in cancer cells was strongly associated with high
VEGF/receptor expression in the vasculature. The high VEGF expression and the aMVD were not associated with the standard microvessel
density (sMVD), as assessed with the monoclonal antibody anti-CD31 and, were not detected in normal tissue. An increased sMVD,
however, was significantly related with the expression thymidine phosphorylase (TP), and also with the nuclear accumulation
of the oncoprotein p53, but neither p53 nor TP was associated with VEGF expression by cancer cells or VEGF/receptor complex
aMVD. In 35% of cancer cases examined, more than 20% of the microvessels assessed with anti-CD31 also expressed the VEGF/KDR
complex. The vasculature of the normal head and neck mucosa did not express the VEGF/KDR complex. There was no association
between VEGF expression or VEGF/receptor complex aMVD and response to chemo-radiotherapy or patient's survival. It is concluded
that activation of the angiogenic pathway VEGF/flk-1(KDR) is tumor specific in a subgroup of locally advanced squamous cell
carcinomas of the head and neck. Selective destruction of this type of vasculature, using immunoconjugates directed against
the VEGF/receptor complex, may prove therapeutically useful for patients with a high tumoral VEGF/flk-1(KDR) activated microvessel
fraction.
This revised version was published online in July 2006 with corrections to the Cover Date. |
| |
Keywords: | angiogenesis flk-1 (KDR) head and neck cancer p53 thymidine phosphorylase VEGF |
本文献已被 SpringerLink 等数据库收录! |
|