N-cadherin antagonists as oncology therapeutics

The cell adhesion molecule (CAM), N-cadherin, has emerged as an important oncology therapeutic target. N-cadherin is a transmembrane glycoprotein mediating the formation and structural integrity of blood vessels. Its expression has also been documented in numerous types of poorly differentiated tumours. This CAM is involved in regulating the proliferation, survival, invasiveness and metastasis of cancer cells. Disruption of N-cadherin homophilic intercellular interactions using peptide or small molecule antagonists is a promising novel strategy for anti-cancer therapies. This review discusses: the discovery of N-cadherin, the mechanism by which N-cadherin promotes cell adhesion, the role of N-cadherin in blood vessel formation and maintenance, participation of N-cadherin in cancer progression, the different types of N-cadherin antagonists and the use of N-cadherin antagonists as anti-cancer drugs.     

Expression and localization of P-, K-, and OB-cadherin in the prepubertal rat ovary.

Classical and atypical cadherins mediate calcium-dependent cell adhesion and play an important role in morphogenetic processes. We have shown, previously, N- and E-cadherin expression in the rat ovary. This expression, however, was not associated with specific follicle-restructuring events such as antrum formation and segregation of mural from cumulus granulosa cells suggesting that other cadherins may serve this function. In this study, RT-PCR and immunostaining techniques showed that three other cadherins are expressed throughout prepubertal ovarian development in the rat: one classical (P-) cadherin, and two atypical (K- and OB-) cadherins. RT-PCR analysis of isolated ovarian tissue compartments (granulosa cells and the residual ovarian tissue) agreed with the immunostaining results. Immunostaining showed P- and K-cadherin expression by granulosa, as well as thecal/interstitial cells, and also in oocytes of primordial follicles. P-cadherin expression was absent in oocytes of follicles in later stages of development compared to K-cadherin, which was found in oocytes at all stages of folliculogenesis. P-, K-, and OB-cadherin were expressed by the ovarian surface epithelial cells of neonatal animals but only P- and OB-cadherin expression were maintained in these cells in 25 day-old animals. Cellular OB-cadherin staining was absent in follicles at all stages of development and its expression was restricted to the ovarian hilar region and portions of the stroma. In summary, cadherin expression and distribution profiles changed during ovarian growth and folliculogenesis suggesting a role for cadherins in organizational and morphogenetic processes within the developing rat ovary.     

Determination of Hexapeptide ALA-ASP-LEU-LYS-PRO-THR by MALDI MS

The hexapeptide ALA-ASP-LEU-LYS-PRO-THR is currently widely used as an active ingredient in commercially available creams. Therefore, the proper analytical procedure to detect this compound is a very important issue. This paper presents the determination of the hexapeptide in solution and in cosmetic formulations by matrix assisted laser desorption ionisation mass spectrometry. We developed a procedure for the selective binding of the low molecular weight peptide by using a two-component matrix which enabled us to characterize the hexapeptide directly without any initial processing. Furthermore, the extensive computer simulations were carried out to assist in this analysis of the MS spectra.