{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86799"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86799","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Role of Fibroblasts in Epithelial to Mesenchymal Transition via Sonic Hedgehog Pathway in Co-Culture Model of Pancreatic Ductal Adenocarcinoma","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Haldankar, Nidhi"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Straubinger, Robert","Pharmacology and Toxicology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-25T23:22:52Z","date_published":"2025-02-25T23:22:52Z","updated_at":"2026-07-27T19:05:37Z","subjects":["pharmacology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86799","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Straubinger, Robert","Pharmacology and Toxicology"]},{"key":"dc:creator","label":"Author","values":["Haldankar, Nidhi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-25T23:22:52Z","2020","2020-08-11 15:09:06"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmacology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86799"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","The sonic hedgehog (SHH) signaling pathway is activated in a paracrine manner in pancreatic ductal adenocarcinoma (PDAC), which mediates the formation of a fibroblast-enriched, desmoplastic stroma. The SHH pathway has been reported to promote an epithelial to mesenchymal transition (EMT), in which the epithelial tumor cells differentiate into a mesenchymal phenotype essential for tumor growth, invasion, and metastasis. However, previous studies in genetically engineered mouse models and patient-derived xenograft mouse models show that inhibition of SHH signaling increased the occurrence of EMT+ tumor cells. We hypothesized that the in vivo paracrine interactions between tumor and stromal cells that lead to enhanced EMT can be recapitulated in vitro in a co-culture model of pancreatic cancer cells and fibroblast cell lines. Phenotypic changes occurring as a result of interaction between the human pancreatic cancer cells and mouse embryonic fibroblasts (NIH 3T3) were assessed in an indirect, conditioned medium culture system, as well as in a direct co-culture model. The expression of epithelial and mesenchymal markers in the tumor cells was examined by western blotting and immunofluorescence staining. Tumor cells exposed to medium conditioned by NIH 3T3 fibroblasts showed higher expression of EMT markers. In the direct co-culture model, in which tumor and fibroblast cells were plated together, the expression levels of EMT markers vimentin and N-cadherin increased in tumor cells compared to their expression in tumor cells cultured alone. Pharmacological inhibition of the sonic hedgehog signaling with a small molecule inhibitor of Smoothened (sHHi) resulted in lower levels of vimentin in the tumor cells. Future studies would expand the investigation to include other major signaling axes in pancreatic cancer, such as fibroblast growth factors.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Role of Fibroblasts in Epithelial to Mesenchymal Transition via Sonic Hedgehog Pathway in Co-Culture Model of Pancreatic Ductal Adenocarcinoma"]}]}],"canonical_facts":{"dc:contributor":["Straubinger, Robert","Pharmacology and Toxicology"],"dc:creator":["Haldankar, Nidhi"],"dc:date":["2025-02-25T23:22:52Z","2020","2020-08-11 15:09:06"],"dc:description":["M.S.","The sonic hedgehog (SHH) signaling pathway is activated in a paracrine manner in pancreatic ductal adenocarcinoma (PDAC), which mediates the formation of a fibroblast-enriched, desmoplastic stroma. The SHH pathway has been reported to promote an epithelial to mesenchymal transition (EMT), in which the epithelial tumor cells differentiate into a mesenchymal phenotype essential for tumor growth, invasion, and metastasis. However, previous studies in genetically engineered mouse models and patient-derived xenograft mouse models show that inhibition of SHH signaling increased the occurrence of EMT+ tumor cells. We hypothesized that the in vivo paracrine interactions between tumor and stromal cells that lead to enhanced EMT can be recapitulated in vitro in a co-culture model of pancreatic cancer cells and fibroblast cell lines. Phenotypic changes occurring as a result of interaction between the human pancreatic cancer cells and mouse embryonic fibroblasts (NIH 3T3) were assessed in an indirect, conditioned medium culture system, as well as in a direct co-culture model. The expression of epithelial and mesenchymal markers in the tumor cells was examined by western blotting and immunofluorescence staining. Tumor cells exposed to medium conditioned by NIH 3T3 fibroblasts showed higher expression of EMT markers. In the direct co-culture model, in which tumor and fibroblast cells were plated together, the expression levels of EMT markers vimentin and N-cadherin increased in tumor cells compared to their expression in tumor cells cultured alone. Pharmacological inhibition of the sonic hedgehog signaling with a small molecule inhibitor of Smoothened (sHHi) resulted in lower levels of vimentin in the tumor cells. Future studies would expand the investigation to include other major signaling axes in pancreatic cancer, such as fibroblast growth factors.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86799"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pharmacology"],"dc:title":["Role of Fibroblasts in Epithelial to Mesenchymal Transition via Sonic Hedgehog Pathway in Co-Culture Model of Pancreatic Ductal Adenocarcinoma"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:37Z"}