P-cadherin in adhesion and invasion: opposite roles in colon and bladder carcinoma.
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.
Van Marck
Veerle
V
Department of Radiotherapy and Nuclear Medicine, Laboratory of Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium. marc1.bracke@ugent.be
Stove
Christophe
C
Jacobs
Koen
K
Van den Eynden
Gert
G
Bracke
Marc
M
D001483:Base Sequence; D015153:Blotting, Western; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D003110:Colonic Neoplasms / Q000473:pathology*; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D015820:Cadherins; D017931:DNA Primers