Utilizing cell line-derived organoids to evaluate the efficacy of a novel LIFR-inhibitor, EC359 in targeting pancreatic tumor stroma
Autor: | Surinder K. Batra, Rakesh Bhatia, Hareesh B. Nair, Christopher Thompson, Sushil Kumar, Bradley R. Hall, Andrew Cannon, Klaus Nickisch, Alejandra Chavez-Riveros, Bindu Santhamma |
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Rok vydání: | 2018 |
Předmět: |
3D model
0301 basic medicine Cancer Research Cell pancreatic ductal adenocarcinoma 03 medical and health sciences Stroma Pancreatic tumor Pancreatic cancer Parenchyma Genetics Organoid Medicine LIF business.industry LIFR medicine.disease 3. Good health Desmoplasia pancreatic stroma 030104 developmental biology medicine.anatomical_structure Cell culture Cancer research medicine.symptom business Research Paper |
Zdroj: | Genes & Cancer |
ISSN: | 1947-6027 |
Popis: | Survival of pancreatic cancer (PC) patient is poor due to lack of effective treatment modalities, which is partly due to the presence of dense desmoplasia that impedes the delivery of chemotherapeutics. Therefore, PC stroma-targeting therapies are expected to improve the efficacy of chemotherapeutics. However, in vitro evaluation of stromal-targeted therapies requires a culture system which includes components of both tumor stroma and parenchyma. We aim to generate a cell line-derived 3D organoids to test the efficacy of stromal-targeted, LIFR-inhibitor EC359. Murine PC (FC1245) and stellate (ImPaSC) cells were cultured to generate organoids that recapitulated the histological organization of PC with the formation of ducts by epithelial cells surrounded by activated fibroblasts, as indicated by CK19 and α-SMA staining, respectively. Analysis by qRT-PCR demonstrated a significant downregulation of markers of activated stroma, POSTN, FN1, MMP9, and SPARC (p |
Databáze: | OpenAIRE |
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