Kawakami M, Furuhata T, Kimura Y, Yamaguchi K, Hata F, Sasaki K, Hirata K
First Dept. of Surgery, Sapporo Medical University, Sapporo, Japan.
J Exp Clin Cancer Res. 2003 Jun;22(2):229-37.
This study was undertaken to determine whether expressions of the vascular endothelial growth factor (VEGF) family (VEGF-A, VEGF-B, VEGF-C, and VEGF-D) are correlated with clinicopathological parameters, with particular reference to lymph node metastasis in colorectal cancer. Total RNA was isolated from 82 surgical specimens of colorectal cancer and matched to normal mucosa with (n = 41) or without (n = 41) lymph node metastasis. The mRNA expression of each VEGF family member was quantified by real-time quantitative (RTQ) RT-PCR assay. VEGF-B and VEGF-C mRNA were significantly higher both in the tumors with lymph node metastasis (p = 0.027 and p = 0.024, respectively) and in tumors with lymphatic invasion (p = 0.042 and p = 0.005, respectively). In contrast, VEGF-D mRNA was down-regulated in tumors with lymphatic involvement (p = 0.047). Among the other clinicopathological factors, we noted that VEGF-A mRNA was higher in tumors with liver metastasis than in those without (p = 0.018) and was higher in tumors with venous invasion than in those without (p = 0.007). The results of this study demonstrate that high levels of VEGF-B, C and low levels of VEGF-D mRNA expression are associated with lymph node metastasis and lymphatic involvement. These results suggest that a balance among VEGF-B, VEGF-C, and VEGF-D might contribute to the lymphangiogenic process and metastasis in colorectal cancer.
本研究旨在确定血管内皮生长因子（VEGF）家族（VEGF-A、VEGF-B、VEGF-C和VEGF-D）的表达是否与临床病理参数相关，特别是与结直肠癌的淋巴结转移相关。从82例结直肠癌手术标本中分离出总RNA，并与有（n = 41）或无（n = 41）淋巴结转移的正常黏膜进行匹配。通过实时定量（RTQ）RT-PCR测定法对每个VEGF家族成员的mRNA表达进行定量。VEGF-B和VEGF-C mRNA在有淋巴结转移的肿瘤中（分别为p = 0.027和p = 0.024）以及有淋巴管侵犯的肿瘤中（分别为p = 0.042和p = 0.005）均显著升高。相比之下，VEGF-D mRNA在有淋巴管受累的肿瘤中下调（p = 0.047）。在其他临床病理因素中，我们注意到有肝转移的肿瘤中VEGF-A mRNA高于无肝转移的肿瘤（p = 0.018），有静脉侵犯的肿瘤中VEGF-A mRNA高于无静脉侵犯的肿瘤（p = 0.007）。本研究结果表明，高水平的VEGF-B、C和低水平的VEGF-D mRNA表达与淋巴结转移和淋巴管受累相关。这些结果提示，VEGF-B、VEGF-C和VEGF-D之间的平衡可能有助于结直肠癌的淋巴管生成过程和转移。
