Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes

Abstract

The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes. ' 2005 Wiley-Liss, Inc.

Effects of VEGFR-3 phosphorylation inhibitor on lymph node metastasis in an orthotopic diffuse-type gastric carcinoma model

“…VEGFR-3 inhibitor for lymph node metastasis M Yashiro et al (Kitadai et al, 2005;Juttner et al, 2006). Ki23057 showed considerable inhibitory activity against autophosphorylation of VEGFR-3 in vitro and in vivo; the IC 50 for VEGFR-3 is 4.3 nM in the cellular assay and 5.4 nM in the cell-free kinase assay.…”

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

“…Expression of VEGF-C in tumor tissue serves as a reliable marker for ongoing tumor lymphangiogenesis and increased risk of regional lymph node metastasis in many cancer types [172,173]. Data for VEGF-D are less consistent suggesting that its ability to promote metastatic spread via lymphatics depends on the investigated cancer type and/ or grade [174][175][176]. The question remains whether VEGF-C and D may alter adhesive properties of both tumor and endothelial cells or modify functional features of lymphatic vessels, thus enhancing tumor cell adhesion to and intravasation into lymphatics.…”

Inhibiting tumor growth of colorectal cancer by blocking the expression of vascular endothelial growth factor receptor 3 using interference vector-based RNA interference

“…Some studies found no relationship between them (18,19). Furthermore, Padera et al (20) has shown that inhibiting VEGFR3 is not effective in treating lymph node metastasis after cells have arrived in the lymph node in this tumor model, but VEGFR3 overexpression of tumor cells, in experimental tumor models, resulted in intratumoral and peritumoral lymphangiogenesis and increased metastasis to the regional lymph nodes (4,5).…”