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Desmoplastic Crosstalk in Pancreatic Ductal Adenocarcinoma Is Reflected by Different Responses of Panc-1, MIAPaCa-2, PaTu-8902, and CAPAN-2 Cell Lines to Cancer-associated/Normal Fibroblasts
Š. Novák, M. Kolář, A. Szabó, Z. Vernerová, L. Lacina, H. Strnad, J. Šáchová, M. Hradilová, J. Havránek, M. Španko, M. Čoma, L. Urban, M. Kaňuchová, N. Melegová, R. Gürlich, J. Dvořák, K. Smetana, P. Gál, P. Szabo
Jazyk angličtina Země Řecko
Typ dokumentu časopisecké články
NLK
Free Medical Journals
od 2004 do Před 2 roky
PubMed Central
od 2016
Europe PubMed Central
od 2016
PubMed
33893076
DOI
10.21873/cgp.20254
Knihovny.cz E-zdroje
- MeSH
- duktální karcinom slinivky břišní metabolismus patologie MeSH
- epitelo-mezenchymální tranzice MeSH
- fibroblasty asociované s nádorem metabolismus patologie MeSH
- fibroblasty metabolismus patologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí MeSH
- nádory slinivky břišní metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) still represents one of the most aggressive cancers. Understanding of the epithelial-mesenchymal crosstalk as a crucial part of the tumor microenvironment should pave the way for therapies to improve patient survival rates. Well-established cell lines present a useful and reproducible model to study PDAC biology. However, the tumor-stromal interactions between cancer cells and cancer-associated fibroblasts (CAFs) are still poorly understood. MATERIALS AND METHODS: We studied interactions between four PDAC cell lines (Panc-1, CAPAN-2, MIAPaCa-2, and PaTu-8902) and conditioned media derived from primary cultures of normal fibroblasts/PDAC-derived CAFs (PANFs). RESULTS: When the tested PDAC cell lines were stimulated by PANF-derived conditioned media, the most aggressive behavior was acquired by the Panc-1 cell line (increased number and size of colonies, remaining expression of vimentin and keratin 8 as well as increase of epithelial-to-mesenchymal polarization markers), whereas PaTu-8902 cells were rather inhibited. Of note, administration of the conditioned media to MIAPaCa-2 cells resulted in an inverse effect on the size and number of colonies, whereas CAPAN-2 cells were rather stimulated. To explain the heterogeneous pattern of the observed PDAC crosstalk at the in vitro level, we further compared the phenotype of primary cultures of cells derived from ascitic fluid with that of the tested PDAC cell lines, analyzed tumor samples of PDAC patients, and performed gene expression profiling of PANFs. Immuno-cyto/histo-chemical analysis found specific phenotype differences within the group of examined patients and tested PDAC cell lines, whereas the genomic approach in PANFs found the key molecules (IL6, IL8, MFGE8 and periostin) that may contribute to the cancer aggressive behavior. CONCLUSION: The desmoplastic patient-specific regulation of cancer cells by CAFs (also demonstrated by the heterogeneous response of PDAC cell lines to fibroblasts) precludes simple targeting and development of an effective treatment strategy and rather requires establishment of an individualized tumor-specific treatment protocol.
BIOCEV 1st Faculty of Medicine Charles University Vestec Czech Republic
Department of Pharmacology Pavol Jozef Šafárik University Košice Slovak Republic
Institute of Anatomy 1st Faculty of Medicine Charles University Prague Czech Republic
Citace poskytuje Crossref.org
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