P‐cadherin in adhesion and invasion: Opposite roles in colon and bladder carcinoma

钙粘蛋白 下调和上调 基因敲除 免疫组织化学 结直肠癌 癌症研究 腺癌 病理 生物 细胞粘附分子 癌症 医学 内科学 细胞培养 免疫学 细胞 基因 生物化学 遗传学
作者
Veerle Van Marck,Christophe P. Stove,Koen Jacobs,Gert Van den Eynden,Marc Bracke
出处
期刊:International Journal of Cancer [Wiley]
卷期号:128 (5): 1031-1044 被引量:56
标识
DOI:10.1002/ijc.25427
摘要

Abstract Neoexpression or upregulation of placental cadherin (P‐cadherin), a member of the classical cadherin family, has previously been described in several carcinomas, such as colorectal and bladder carcinomas. In this study, we combined two different approaches, immunohistochemistry of tumor samples and in vitro knockdown of P‐cadherin, to gain a better insight into the role of P‐cadherin in these types of cancer. First, we performed immunohistochemistry for P‐ and E‐cadherins in a series of 52 colorectal adenocarcinomas, including well, moderately and poorly differentiated (WD, MD, and PD) tumors. Decrease or loss of P‐cadherin neoexpression was significantly associated with a higher tumor grade and could discriminate WD from MD and/or PD tumors ( p < 0.001). E‐cadherin, on the other hand, was strongly expressed at the membrane of most WD (18 of 19) and MD tumors (15 of 19). Downregulation correlated significantly with the PD phenotype ( p ≤ 0.001). In a second approach, we transiently or stably knocked down P‐cadherin in HT‐29 colon adenocarcinoma cells. This led to decreased intercellular adhesion and to an increased migratory and long‐term invasive phenotype compared with control HT‐29 cells, suggesting that P‐cadherin acts as a proadhesive and anti‐invasive/antimigratory molecule in colon carcinoma cells. Contrasting with these results and illustrating the context‐specific function of P‐cadherin were our results obtained in RT‐112 bladder carcinoma cells. Stable knockdown of P‐cadherin in RT‐112 cells diminished invasion and migration, and promoted intercellular adhesion.
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