P-cadherin expression in breast cancer: a review

Abstract

P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumour aggressiveness. In addition, expression of P-cadherin is well established as an indicator of poor prognosis in human breast cancer, which has stimulated our interest in studying its role in this setting. This review describes the most important findings on P-cadherin expression and function in normal mammary tissue and breast cancer cells, emphasizing that further research is required to elucidate the role played by this protein in human mammary tumours. IntroductionClassical cadherins, such as E-cadherin, N-cadherin and Pcadherin, are the best characterized subgroup of adhesion proteins; they mediate calcium-dependent cell-cell bonds when they are localized to the adherens-type junctions. These cellular structures are found near to the apical surface of polarized epithelial cells, where E-cadherin (or epithelial cadherin) is the typical adhesion molecule present. However, other cadherins are found in similar structures in various cell types [1]. P-cadherin (or placental cadherin) was the third classical cadherin to be identified and characterized in the mouse visceral endoderm cell line PSA5-E [2,3], and it is this protein that constitutes the main subject of this review. Despite its name, P-cadherin is not expressed in human placenta [4]; its name results from the fact that this molecule was originally observed to be highly expressed in mouse placenta throughout pregnancy [2,4].The gene encoding P-cadherin (CDH3) is far less well characterized than is CDH1 (the gene that encodes E-cadherin), although they share 66% homology. It also maps to chromosome 16q22.1, a region that contains a cluster of several cadherin genes, just 32 kilobases upstream of the gene encoding human E-cadherin [5,6]. Mutations in the CDH3 gene have been reported to be responsible for congenital hypotrichosis associated with juvenile macular dystrophy, which is a rare autosomal-recessive disorder characterized by abnormal growth of scalp hair, followed by progressive macular retinal degeneration that leads to early blindness [7].The mature P-cadherin glycoprotein has a molecular weight of 118 kDa, and its structure is similar to that of classical cadherins but different from those of E-cadherin and Ncadherin in terms of immunological specificity and molecular mass [2]. It is comprised of three distinct domains (extracellular, transmembrane and cytoplasmic) and it mainly, but not exclusively, promotes homotypic interactions (between cadherins of the same type) [1,2]. The aminoterminal domain is essential for the creation of lateral dimmers that act together in a zipper-like structure between neighbouring cells (Figure 1) [8].The function and strength of P-cadherin mediated adhesion probably depends on its dynamic association with a group of cytoplasmic molecules, called catenins. These molecules serve to link the cadherin cytoplasmic t...

Cadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian cancer

“…Unlike E-cadherin, P-cadherin can promote motility and invasion in carcinoma cells. For example, expression of P-cadherin correlates with metastatic disease and poor prognosis of breast cancer and pancreatic carcinomas (Taniuchi et al, 2005;Paredes et al, 2007). Likewise, P-cadherin is frequently upregulated in ovarian cancer cells and increased with tumor progression (Patel et al, 2003).…”

Co-Activation of Epidermal Growth Factor Receptor and c-MET Defines a Distinct Subset of Lung Adenocarcinomas

“…44 P-cadherin has also been reported to promote the motility of pancreas cancer, 45 and its expression is an indicator of poor outcome in breast cancer. 46 Cox-2 is a rate-limiting enzyme in the production of prostaglandins. 23 Overexpression of cox-2 in cancer has been reported in numerous studies, and the enzyme plays an important role in tumor angiogenesis and survival.…”

P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer

“…P-cadherin is localized in placenta, whereas E-cadherin and N-cadherin are found in epithelial and neural tissues, respectively. [3][4][5] P-cadherin has been shown to be crucial for orderly progression of terminal differentiation of the epidermis, 6 and P-cadherin-mediated adhesion seems to determine mammary gland growth control and maintenance of an undifferentiated state in embryogenesis. 7 E-cadherin and P-cadherin have important roles in the architecture, function, and differentiation of the normal adult non-lactating mammary gland.…”

“…E-cadherin is expressed by both luminal and myoepithelial cells, whereas P-cadherin is restricted to myoepithelial/basal cells in normal breast tissue. 5,8,9 During late pregnancy and lactation, P-cadherin is secreted by epithelial cells, and its soluble fragment is frequently found in human milk.…”