Downregulation of EphA1 in colorectal carcinomas correlates with invasion and metastasis

Abstract

The Eph gene family has important roles in the developmental processes and may also be involved in the initiation, progression, and metastasis of certain types of cancers. In the present study, quantitative real-time reverse-transcriptase PCR was performed to detect the expression of EphA1 transcript in 5 colon cancer cell lines and 75 colorectal carcinomas. Immunohistochemical staining was used to check the expression of EphA1 protein in 20 colorectal adenomas and in 111 colorectal carcinomas specimens. EphA1 protein expression was not completely consistent with transcript expression. EphA1 protein was expressed in all adenomas and reduced in 54% colorectal cancers. Reduced expression of EphA1 protein occurred more often in male patients (P ¼ 0.028) and in patients with poor differentiation (P ¼ 0.027), greater depth of wall invasion (P ¼ 0.003), lymph node metastasis (P ¼ 0.034), and advanced tumor stage (P ¼ 0.003). Patients with reduced EphA1 expression had a poor overall survival (P ¼ 0.059). Reduced EphA1 expression in patients over 55 years or with rectal cancers and sigmoid colon cancers is associated with a poor overall survival (P ¼ 0.034 and 0.015, respectively). Our data indicate that the EphA1 may play different roles during the different stages of colorectal carcinoma progression.

Effects of Macrophage Metalloelastase on the Basic Fibroblast Growth Factor Expression and Tumor Angiogenesis in Murine Colon Cancer

“…Paraffin-embedded tumor sections(thickness of sectioning is 2 lm [16] were incubated with antibodies against mouse MME (1:100; a goat antibody, Santa Cruz, CA, USA), mouse bFGF (1:150, a sheep antibody, Novus Biologicals, Littleton, CO, USA), mouse CD34 (1:150; a goat antibody, Santa Cruz) and a biotinylated rabbit anti-goat IgG (Boster Biotech, China). Immunostaining for MME or bFGF was considered positive when an unequivocal brown staining of the cytoplasm was observed in CT-26 tumor cells.…”

Eph-dependent cell-cell adhesion and segregation in development and cancer

“…Similarly, EphA1 is overexpressed in earlier stages of CRC, but down-regulated in further advanced carcinomas, a trend that is also associated with poor survival [194,195]. Gain-of-function mutations in the Wnt pathway are strongly implicated in the initiation of CRC and at the same time responsible for up-regulated EphB expression [196].…”

Expression of EphA1 in gastric carcinomas is associated with metastasis and survival

“…An inverse correlation has been found between methylation of CpG islands in the 3'-CG-rich region and EphA1 expression in colorectal cancers (18). We designed a set of methylation specific PCR (MSP) primers for 3'-CG-rich region to detect methylated and unmethylated EphA1 DNA, and we detected methylated EphA1 DNA in five colon cancer cell lines (17). In the present study we used MSP to analyze the methylation status of EphA1 in 38 fresh gastric carcinoma tissues (each including normal tissue and tumor tissue).…”

“…However, the role of EphA1 in the carcinogenesis of digestive tract tumors is unknown. We previously reported finding correlations between down-regulation of EphA1 in colorectal carcinomas and invasion and metastasis, and that reduced EphA1 expression is associated with poor overall survival (17), while another study demonstrated that epigenetic silencing of EphA1 expression in colorectal cancer is correlated with poor survival (18). In the present study we evaluated expression of EphA1 in a set of gastric carcinomas and analyzed its association with clinicopathological parameters and survival.…”