Abstract
Vascular endothelial growth factor (VEGF) is a well known factor that induces angiogenesis. Four isoforms, i.e. VEGF206, 189, 165, and 121, have been identified. We examined the isoform patterns of VEGF mRNA using reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. All the colon cancers examined expressed VEGF121. The isoform patterns were classified into three groups: type 1, VEGF121; type 2, VEGF121 + VEGF165; type 3, VEGF121 + VEGF165 + VEGF189. Three of the 61 colon cancers examined showed type 1 expression, 26 showed type 2 expression and 32 showed the type 3 pattern. The patients with liver metastases showed the type 3 isoform expression pattern at a significantly higher incidence (12 of 16, 75%) than those without liver metastasis (20 of 45, 44%) (P=0.036). The type 3 isoform pattern was significantly associated with M1 stage (P=0.019). The patients with colon cancer and the type 3 isoform pattern showed significantly poor prognosis (P < 0.01, Cox-Mantel). The colon cancers with the type 3 pattern showed a significantly higher involvement of veins (P=0.006). These observations suggest that the aberrant type 3 expression pattern of VEGF189 mRNA isoforms is correlated with liver metastasis, M stage, and poor prognosis in colon cancer.
MeSH Terms
Adenocarcinoma/mortality,pathology,secondary,surgery
Adenocarcinoma, Mucinous/mortality,pathology,secondary,surgery
Colonic Neoplasms/metabolism,mortality,pathology,surgery
Endothelial Growth Factors/biosynthesis
Female
Genes, ras
Humans
Liver Neoplasms/metabolism,pathology,secondary,surgery
Lymphokines/biosynthesis
Male
Middle Aged
Mutation
Neoplasm Staging
Polymerase Chain Reaction
Predictive Value of Tests
Prognosis
Proto-Oncogene Proteins/biosynthesis
RNA, Messenger/biosynthesis
Receptor Protein-Tyrosine Kinases/biosynthesis
Receptors, Growth Factor/biosynthesis
Receptors, Vascular Endothelial Growth Factor
Retrospective Studies
Survival Rate
Time Factors
Transcription, Genetic
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factors
Chemicals
Endothelial Growth Factors
Lymphokines
Proto-Oncogene Proteins
RNA, Messenger
Receptors, Growth Factor
VEGFA protein, human
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Receptor Protein-Tyrosine Kinases
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-1
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Tokunaga T
Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Oshika Y
Abe Y
Ozeki Y
Sadahiro S
Kijima H
Tsuchida T
Yamazaki H
Ueyama Y
Tamaoki N
Nakamura M
References (21)
21 references, click to expand
-
Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid.
Science. 1983 Feb 25;219(4587):983-5
PMID: 6823562
-
Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by cell density.
Cancer Res. 1996 Sep 1;56(17):3891-4
PMID: 8752153
-
Vascular permeability factor, an endothelial cell mitogen related to PDGF.
Science. 1989 Dec 8;246(4935):1309-12
PMID: 2479987
-
Higher frequency of point mutations in the c-K-ras 2 gene in human colorectal adenomas with severe atypia than in carcinomas.
Jpn J Cancer Res. 1991 Mar;82(3):245-9
PMID: 1708754
-
Effects of a variety of cytokines and inducing agents on vascular permeability factor mRNA levels in U937 cells.
Biochem Biophys Res Commun. 1991 Oct 31;180(2):572-8
PMID: 1719968
-
The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA.
Mol Endocrinol. 1991 Dec;5(12):1806-14
PMID: 1791831
-
Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors.
Mol Biol Cell. 1992 Feb;3(2):211-20
PMID: 1550962
-
Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms.
J Biol Chem. 1992 Dec 25;267(36):26031-7
PMID: 1464614
-
Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms.
J Clin Invest. 1993 Jan;91(1):153-9
PMID: 8380810
-
Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract.
Cancer Res. 1993 Oct 1;53(19):4727-35
PMID: 8402650
-
The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.
Mol Biol Cell. 1993 Dec;4(12):1317-26
PMID: 8167412
-
Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer.
Hum Pathol. 1995 Jan;26(1):86-91
PMID: 7821921
-
Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis.
J Clin Invest. 1995 Apr;95(4):1789-97
PMID: 7535799
-
Expression of vascular endothelial growth factor and its receptors flt and KDR in ovarian carcinoma.
J Natl Cancer Inst. 1995 Apr 5;87(7):506-16
PMID: 7707437
-
VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells.
J Biol Chem. 1995 May 12;270(19):11322-6
PMID: 7744769
-
Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.
Am J Pathol. 1995 May;146(5):1029-39
PMID: 7538264
-
Platelet factor-4 inhibits the mitogenic activity of VEGF121 and VEGF165 using several concurrent mechanisms.
J Biol Chem. 1995 Jun 23;270(25):15059-65
PMID: 7797488
-
Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.
Cancer Res. 1995 Sep 15;55(18):3964-8
PMID: 7664263
-
Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis.
Cancer Res. 1995 Oct 15;55(20):4575-80
PMID: 7553632
-
Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma.
Cancer Res. 1996 Jul 1;56(13):3004-9
PMID: 8674055
-
Vascular endothelial growth factor is a secreted angiogenic mitogen.
Science. 1989 Dec 8;246(4935):1306-9
PMID: 2479986