Expression of Vascular Endothelial Growth Factor D Is Associated with Lymph Node Metastasis in Human Colorectal Carcinoma

Abstract

Objective: Expression of vascular endothelial growth factor (VEGF)-D by tumors is associated with metastasis to lymph nodes in mice. However, there are few reports concerning the clinical significance of VEGF-D protein in human carcinoma. Methods: After confirming production of VEGF-D by eight colorectal carcinoma cell lines, we investigated relationships between the expression of VEGF-D protein, lymph node metastasis and postoperative survival in 83 colorectal carcinoma patients. mRNA levels in cell lines were evaluated using the real-time reverse transcriptase-polymerase chain reaction, and protein was detected by Western blotting in cell lines and by immunohistochemistry in resected tissues using an antibody recognizing the processed form of the molecule. Results: Immunohistochemistry showed VEGF-D-positive staining in 26 of the 83 carcinomas (31%). There was a significant relationship between the presence of VEGF-D protein and the incidence of lymph node metastasis (p < 0.01). Multivariate logistic regression analysis revealed that VEGF-D protein expression was an independent factor affecting lymph node metastasis (p < 0.01). Nonetheless, the presence or absence of VEGF-D protein had no significant impact on the survival of the patients (p = 0.15). Conclusion: These results suggest that the expression of VEGF-D protein could be useful in predicting the nodal status of colorectal carcinoma patients.

Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer

“…Vascular endothelial growth factor (VEGF) has been nominated as one of the triggers of angiogenesis. VEGF expression has also demonstrated a strong association with the presence of lymph node metastasis [41,42]. Moreover, VEGF stimulation reportedly causes increased expression of survivin [43].…”

Vascular endothelial growth factor (VEGF) signaling in tumor progression

“…VEGF-D is up-regulated in breast [86], colorectal [87], gastric [79], and thyroid [88] carcinomas, cervical intraepithelial neoplasia [89], glioblastoma [90], and melanoma [91]. Its expression correlates with lymph node metastasis in colorectal [92], lung [93], and ovarian carcinomas [94]. VEGF-D signaling thus represents a potential anti-cancer and antimetastasis target.…”

Expression of vascular endothelial growth factor C and chemokine receptor CCR7 in gastric carcinoma and their values in predicting lymph node metastasis

“…A recent study by Orlandini et al [13] demonstrated that β-catenin was a negative regulator of VEGF-D mRNA stability, therefore VEGF-D expression might only be responsible for the nodal metastatic behavior in tumors that have lost or reduced expression of β-catenin. In addition, there was apparent discrepancy of VEGF-D expression in tumors reported by different authors [14][15][16][17][18] . Thus, here we only investigate the role of VEGF-C in promoting lymph node metastasis in gastric carcinoma.…”