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Cadherin Expression (cadherin + expression)
Selected AbstractsRhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cellsDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2004Isabel Laplante Abstract RhoGTPases regulate actin-based signaling cascades and cellular contacts. In neurogenesis, their action modulates cell migration, neuritogenesis, and synaptogenesis. Murine P19 embryonal stem cells differentiate to neurons upon aggregation in the presence of retinoic acid, and we previously showed that RhoA and Cdc42 RhoGTPases are sequentially up-regulated during neuroinduction, suggesting a role at this very early developmental stage. In this work, incubation of differentiating P19 cells with C3 toxin resulted in decreased aggregate cohesion and cadherin protein level. In contrast, C3 effects were not observed in cells overexpressing recombinant dominant active RhoA. On the other hand, C3 did not affect cadherin in uninduced cells and their postmitotic neuronal derivatives, respectively expressing E- and N-cadherin. RhoA is thus influential on cell aggregation and cadherin expression during a sensitive time window that corresponds to the switch of E- to N-cadherin. Cell treatment with Y27632 inhibitor of Rho-associated-kinase ROCK, or advanced overexpression of Cdc42 by gene transfer of a constitutively active form of the protein reproduced C3 effects. RhoA-antisense RNA also reduced cadherin level and the size of cell aggregates, and increased the generation of fibroblast-like cells relative to neurons following neuroinduction. Colchicin, a microtubule disrupter, but not cytochalasin B actin poison, importantly decreased cadherin in neurodifferentiating cells. Overall, our results indicate that the RhoA/ROCK pathway regulates cadherin protein level and cell-cell interactions during neurodetermination, with an impact on the efficiency of the process. The effect on cadherin seems to involve microtubules. The importance of correct timing of RhoA and Cdc42 functional expression in neurogenesis is also raised. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 289,307, 2004 [source] Cadherin expression pattern in melanocytic tumors more likely depends on the melanocyte environment than on tumor cell progressionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Sven Krengel Background:, Adhesion molecules have been assigned an important role in melanocytic tumor progression. By the loss of E-cadherin, melanocytes might escape the control of neighbouring keratinocytes. Although in vitro data support this hypothesis, there are yet no conclusive immunohistochemical results on cadherin expression in melanocytic tumors. Objective:, To gain detailed insight in the expression of cadherins and their cytoplasmic binding partners, the catenins, in various types of benign and malignant melanocytic neoplasms. Methods:, Immunohistochemical analysis of the expression of E-, P-, and N-cadherin and ,-, ,-, and ,-catenin in compound and dermal nevi, Spitz nevi, blue nevi, ultraviolet B (UVB)-irradiated nevi, and malignant melanomas of various tumor thickness. Results:, In both nevi and melanomas, E-cadherin expression in melanocytic cells decreased, following a gradient from junctional to deeper dermal localization. The pattern of E-cadherin expression was more heterogeneous in melanomas than in nevi. In some melanomas, E-cadherin was only weakly positive in the epidermal tumor cells. P-cadherin expression was similar to that of E-cadherin. N-cadherin expression in melanocytic lesions was a rare finding, however, a small percentage of melanomas showed expression in some cell nests. Some Spitz nevi exhibited strong N-cadherin immunoreactivity. Most melanocytic cells were ,- and ,-catenin-positive and ,-catenin-negative. UVB irradiation did not influence the expression of cadherins and catenins in melanocytic nevi in vivo. Conclusions:, It is presumed that the gradual loss of E-cadherin expression represents a reaction of melanocytic cells to altered conditions in the dermal environment, e.g. lack of contact to keratinocytes, or new contact with dermal extracellular matrix molecules, respectively. Melanoma cells apparently are less dependent on these environmental factors and, therefore, show a more heterogeneous expression pattern. This might be of importance for the adaptation of the tumor cells to local requirements. However, in view of our results, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven. [source] Enhanced differentiation of embryonic stem cells using co-cultivation with hepatocytesBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2008Rebecca N. Moore Abstract We examined the effects of co-cultivated hepatocytes on the hepatospecific differentiation of murine embryonic stem (ES) cells. Utilizing an established mouse ES cell line expressing high or low levels of E-cadherin, that we have previously shown to be responsive to hepatotrophic growth factor stimulation (Dasgupta et al., 2005. Biotechnol Bioeng 92(3):257,266), we compared co-cultures of cadherin-expressing ES (CE-ES) cells with cultured rat hepatocytes, allowing for either paracrine interactions (indirect co-cultures) or both juxtacrine and paracrine interactions (direct co-cultures, random and patterned). Hepatospecific differentiation of ES cells was evaluated in terms of hepatic-like cuboidal morphology, heightened gene expression of late maturation marker, glucose-6-phosphatase in relation to early marker, alpha-fetoprotein (AFP), and the intracellular localization of albumin. Hepatocytes co-cultured with growth factor primed CE-ES cells markedly enhanced ES cell differentiation toward the hepatic lineage, an effect that was reversed through E-cadherin blockage and inhibited in control ES cells with reduced cadherin expression. Comparison of single ES cell cultures versus co-cultures show that direct contact co-cultures of hepatocytes and CE-ES cells maximally promoted ES cell commitment towards hepatodifferentiation, suggesting cooperative effects of cadherin-based juxtacrine and paracrine interactions. In contrast, E-cadherin deficient mouse ES (CD-ES) cells co-cultured with hepatocytes failed to show increased G6P expression, confirming the role of E-cadherin expression. To establish whether albumin expression in CE-ES cells was spatially regulated by co-cultured hepatocytes, we co-cultivated CE-ES cells around micropatterned, pre-differentiated rat hepatocytes. Albumin localization was enhanced "globally" within CE-ES cell colonies and was inhibited through E-cadherin antibody blockage in all but an interfacial band of ES cells. Thus, stem cell based cadherin presentation may be an effective tool to induce hepatotrophic differentiation by leveraging both distal/paracrine and contact/juxtacrine interactions with primary cells of the liver. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc. [source] P-cadherin expression reduced in squamous cell carcinoma of the oral cavityCANCER, Issue 5 2005An indicator of poor prognosis Abstract BACKGROUND The loss of cadherin expression has been shown to correlate to the invasion and metastasis of many types of carcinomas. The purpose of the current study was to evaluate whether the impaired expression of E-cadherin (E-cad) and P-cadherin (P-cad) correlated with the clinical evolution and prognosis of oral squamous cell carcinoma (OSCC). METHODS The authors used immunohistochemical methods to analyze the expression pattern of E-cad and P-cad in healthy oral mucosa, in oral carcinoma in situ (CIS), and in surgical samples of 50 patients with the early stages (Stages I,II) of OSCC. RESULTS E-cad showed weak expression in the basal layer of the healthy oral mucosa and reduced expression in patients with oral CIS. P-cad expression was conserved on the basal and suprabasal layers of the healthy mucosa and, also, in the CIS. In the group of patients with OSCC, univariate analysis demonstrated that reduced expression of E-cad or P-cad correlated significantly with locoregional disease recurrence in the follow-up (P = 0.03 and P = 0.01, respectively). However, only the reduction in the expression of P-cad emerged as an independent prognostic marker in the multivariate analysis (P = 0.04, hazard ratio = 8.06). CONCLUSIONS These findings suggested that a decrease in E-cad and/or P-cad expression may contribute to the invasive potential of early OSCC. According to the current data, P-cad expression may be a potential independent prognostic factor in patients with OSCC. Cancer 2005. © 2005 American Cancer Society. [source] | |||||||||||||