title: Vascular endothelial growth factors and receptors in colorectal cancer: implications for anti-angiogenic therapy.
abstract: There are conflicting associations between growth factor expression and clinicopathological variables in colorectal cancer. This study aimed to define the expression of members of the VEGF family and the receptor, VEGFR2, in primary and metastatic sites of colorectal cancer and their relationship to metastatic potential. Thirty colorectal cancers, 12 lymph node metastases and 9 liver metastases were immunostained for VEGF-A, VEGF-C, VEGF-D and VEGFR2. VEGFR2 was expressed by endothelial cells and by the malignant epithelium. VEGF-C and VEGFR2 were co-expressed in the same territory and correlated throughout the primary tumour and in metastatic lymph nodes, but not in liver metastases. Their expression at the invasive tumour edge correlated with expression in metastatic nodes. The benefit of anti-VEGF antibodies might be increased by directing additional therapies against VEGF-C or against the kinase receptors to target redundancy in the system. A component of the therapeutic benefit might be due to a direct anti-tumour effect as well as an anti-angiogenic effect.
authors.affiliation: Department of Surgery, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Duff
authors.forename: Maria
authors.initials: M
authors.lastname: Jeziorska
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Rosa
authors.forename: Shant
authors.initials: S
authors.lastname: Kumar
authors.forename: Najib
authors.initials: N
authors.lastname: Haboubi
authors.forename: David
authors.initials: D
authors.lastname: Sherlock
authors.forename: Sarah T
authors.initials: ST
authors.lastname: O'Dwyer
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Jayson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000517:prevention & control; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors; D040301:Vascular Endothelial Growth Factor Receptor-2