Liu Shaohua, Zeng Yunjie, Li Yunhua, Guo Wenying, Liu Jiali, Ouyang Nengtai
The laboratory of Surgery, Pingxiang Health School, Pingxiang, Jiangxi province, China.
Tumour Biol. 2014 Jul;35(7):6397-404. doi: 10.1007/s13277-014-1852-x. Epub 2014 Mar 28.
Vasoactive intestinal peptide (VIP) is a neurotransmitter that primarily functions as a vasodilator. VIP plays its role through binding to its receptors known as VIP/pituitary adenylate cyclase-activating peptide receptors (VPACs). In this study, we examined the expression of VPAC1 in human colon cancer tissues, analyzed the relationship between VPAC1 expression and cancer malignancy, and explored the possible mechanisms using immunohistochemistry and immunofluorescence double staining. The results showed that (1) poorly differentiated colon cancers have significantly higher VPAC1 expression than well-differentiated colon cancers do (p < 0.01); (2) phospho-epithelial growth factor receptor (EGFR) overexpression/activation in the cytoplasm of cancer cells is related to VPAC1 overexpression; (3) blood vessels surrounding colon cancer have significantly more VPAC1-positive than normal colon mucosa does; (4) tumor-associated macrophages (TAMs) of colon cancer have a higher level of VPAC1 expression than macrophages in normal colon mucosa do. These data suggest that VPAC1 overexpression is associated with poorer differentiation of colon cancer, which is likely caused by subsequent EGFR activation in cancer cells. In addition, VPAC1 overexpression in both blood vessels and macrophages in tumors may also play an important role in the development of aggressive cancer.
血管活性肠肽（VIP）是一种主要作为血管舒张剂起作用的神经递质。VIP通过与称为VIP/垂体腺苷酸环化酶激活肽受体（VPACs）的受体结合来发挥其作用。在本研究中，我们使用免疫组织化学和免疫荧光双重染色检查了人结肠癌组织中VPAC1的表达，分析了VPAC1表达与癌症恶性程度之间的关系，并探讨了可能的机制。结果表明：（1）低分化结肠癌的VPAC1表达明显高于高分化结肠癌（p<0.01）；（2）癌细胞胞质中磷酸化表皮生长因子受体（EGFR）的过表达/激活与VPAC1的过表达有关；（3）结肠癌周围血管的VPAC1阳性表达明显多于正常结肠黏膜；（4）结肠癌的肿瘤相关巨噬细胞（TAM）中VPAC1的表达水平高于正常结肠黏膜中的巨噬细胞。这些数据表明，VPAC1过表达与结肠癌的低分化有关，这可能是由癌细胞随后的EGFR激活引起的。此外，肿瘤血管和巨噬细胞中VPAC1的过表达也可能在侵袭性癌症的发展中起重要作用。
