Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma.
Vascular endothelial growth factors (VEGF) are secreted by many tumor types, and are believed to affect tumor growth by promoting angiogenesis through binding to their receptors present on vascular endothelium. Recently, mRNA for VEGF-C the ligand for VEGFR-3, was found to be up-regulated in colorectal adenocarcinoma (CRC). The aim of this work was to determine: 1) the distribution of VEGF-C and VEGFR-3 in CRC, and 2) the biological significance of such expression. Sections of formalin-fixed and paraffin-embedded tissues from 56 CRC were immunohistochemically stained for VEGF-C and VEGFR-3. The type and percent of positive cells was recorded. Survival analysis was performed using the Kaplan-Meier method. All CRC were positive for VEGF-C which was present in the cancer cells themselves, as well as in stromal cells. Normal colon epithelium was usually negative. Only ten (17%) of the 56 CRC completely lacked VEGFR-3 expression. VEGFR-3 immunoreactivity was detected in <25% of the cancer cells in 22 cases and in >25% of the cells in 34 cases. Expression of VEGFR-3 in >25% of the cancer cells was associated with significantly poorer overall survival (p<0.05), but not with lymph node metastasis or depth of tumor invasion. Our results suggest that VEGFs promote cancer growth not only by stimulating angiogenesis, but also by acting on receptors present on the cancer cells themselves.
Witte
Deborah
D
Department of Pathology, Baylor College of Medicine and The Methodist Hospital, Houston, TX 77030, USA.
Thomas
Abraham
A
Ali
Najeeba
N
Carlson
Nicole
N
Younes
Mamoun
M
D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D013737:Testis / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D017978:Receptors, Growth Factor; D042582:Vascular Endothelial Growth Factor C; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3