Epithelial-to-mesenchymal transition (EMT) is a biological function important in normal cellular processes such as embryonic development and wound healing. In cancer it is thought that the tumor cell machinery can re-activate these normal pathways resulting in more aggressive and invasive tumors. The loss of E-cadherin and the gain of vimentin are hallmarks which identify the process of EMT and have been shown to correlate with poor prognosis in multiple solid tumor types. While many preclinical models are utilized to evaluate mechanisms of tumorigenesis few in vivo models evaluating parameters of EMT have been described. The EL1-luc/EL1-SV40 T-antigen transgenic mouse represents a model of pancreatic cancer whereby mice develop tissue specific, spontaneous and bioluminescent pancreatic tumors. To evaluate whether EMT occurs in the EL1-luc/EL1-SV40 T-antigen model in vivo, we collected primary pancreatic tissue from male mice between 10 and 21 weeks of age. The tissue was formalin fixed, paraffin embedded and then utilized for histopathological endpoints such as Hemotoxylin and Eosin staining as well as immunohistochemistry for markers known to be involved in EMT such as E-cadherin and vimentin. We found the tumors to express both markers and become very heterogeneous over time. In early tumors E-cadherin expression is membrane localized and very high. Over time there are areas of the tumors that have reduced or lost E-cadherin expression. Vimentin expression was highly variable but when present tended to be highly expressed. In many of the later stage tumors there was substantial heterogeneity reflected by the appearance of multiple cell types within a tumor. We utilized the Aperio (Aperio Technologies, Vista, CA) slide scanner and software system to evaluate serial sections of tumor samples and found that in some sections of the tumor E-cadherin is present and vimentin is absent, whereas in other areas of the tumor vimentin is present in the absence of E-cadherin. Additionally, we identified areas of the tumor that seem to be expressing both markers which suggests that the EL1-luc/EL1-SV40 T-antigen transgenic mouse may recapitulate many aspects of EMT observed in vivo, thus offering a model system to study the signaling and molecular changes necessary for this process during cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4160.
A personalized approach towards the therapy of colorectal carcinoma is critical for a successful outcome. In recent years, direct transfer xenograft models (or the “tumor graft”) have proven to be highly predictive and are being adapted in clinical practice. However, direct drug evaluation in tumor graft models for each individual patient is not feasible due to time and cost constraints. Predictive biomarker discovery is an extremely promising application of the tumor graft model, since the discovered biomarker signatures will direct therapy choice in a much broader patient population. In collaboration with the Catholic Health Initiatives Center for Translational Research we at Caliper Life Sciences have established a collection of tumor graft samples of primary human colorectal carcinomas. All samples were collected fresh from consenting patients following an IRB-approved protocol and implanted in vivo on the day of surgical tumor resection. Tumors were grafted either orthotopically or subcutaneously in female NIH-III mice. We present here the results of a comparative study of gene and protein expression profiles for the primary tumor (clinical samples) and the direct transfer xenografts. These data will be correlated with drug sensitivity profiles generated by using the same samples. The resulting data sets will be used to characterize predictive biomarker signatures that will be a valuable tool for selection of the most effective therapy tailored to the individual patient. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1319. doi:1538-7445.AM2012-1319
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.