The intercellular adhesion molecule, cadherin-10, is a marker for human prostate luminal epithelial cells that is not expressed in prostate cancer

Abstract

During the normal turnover of prostate epithelium, stem cells in the basal cell layer produce an intermediate cell population that gives rise to fully differentiated secretory luminal cells. This process is extensively studied in relation to the development of prostate disease, in particular, to elucidate the origin and nature of prostate cancer. We previously showed that the mRNA of a poorly characterised intercellular adhesion molecule, cadherin-10, is strongly expressed in human prostate. Using anticadherin-10 antibodies, immunohistochemistry, and confocal microscopy, we have examined the pattern of cadherin-10 expression in relation to human prostate epithelial differentiation markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival paraffin-embedded and fixed-frozen histopathological specimens in individual and serial sections. In nonneoplastic prostate, E-cadherin is expressed by all basal and luminal epithelial cells, while cadherin-10 is variably expressed in luminal cells where it is colocalised with E-cadherin at basolateral plasma membranes. Cadherin-10 is absent in CK14-and/or CD44-positive basal cells, but is expressed in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19-positive intermediate/luminal cells, but not CK19-positive basal cells. Small foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10 expression is low or undetectable. These findings suggest that the expression of cadherin-10 is associated with the later stages of differentiation of luminal secretory cells, indicating a specific role in secretory cell terminal differentiation. While prostate cancer cells express secretory cell markers (eg, CK18, prostate-specific antigen) and the more generally expressed E-cadherin, their failure to express cadherin-10 further emphasises a role for this cadherin in normal prostate organisation and function.

Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers

“…The missense mutation V1576F is located in the SET domain; one nonsense mutation, R839*, is a truncating mutation upstream of the SET domain, and two nonsense mutations, Q1981* and K2067*, are truncating mutation upstream of the WW domain. In addition to known cancer driver genes such as ERBB2 (6% of cases), NRAS (3%), MET (3%), PIK3CA (1%), AKT2 (1%), TSC1 (1%), and ERBB4 (1%), several putative cancer genes were identified, such as PTPRC [23], SYNE2 [24], GRIN2A [25], and CDH10 [26]. The mutation pattern is summarized in Figure 2B.…”

Semaphorin-7a reverses the ERF-induced inhibition of EMT in Ras-dependent mouse mammary epithelial cells

“…Some of the identified genes were previously found to be involved in EMT or TGF-β signaling, like Cadherin 10 and Forkhead F2 (Aitola et al. , 2000; Walker et al. , 2008).…”

Alterations of type II classical cadherin, cadherin‐10 (CDH10), is associated with pancreatic ductal adenocarcinomas

“…Our data indicate that CDH10 protein expression is altered in PDAC. CDH10 expression was previously shown in normal human prostate luminal epithelial cells but was absent in prostate cancer . The authors developed their own antisera to CDH10, and concluded that expression of CDH10 was involved in a specific role of secretory cell terminal differentiation.…”