Folfirinox-dependent reprogramming of macrophages by primary pancreatic cancer CAFs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA940346 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23683200_1.fastq.gz | Fastqsanger.gz | |||
| SRR23683200_2.fastq.gz | Fastqsanger.gz | |||
| SRR23683201_1.fastq.gz | Fastqsanger.gz | |||
| SRR23683201_2.fastq.gz | Fastqsanger.gz | |||
| SRR23683190_1.fastq.gz | Fastqsanger.gz |
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Project description:The pancreatic cancer tumor microenvironment is dominated primarily by cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs). The interecellular dialogue between CAFs and TAMs and the resulting impact on chemoresistance, specifically to Folfirinox, remains poorly understood. In this study, we sought to understand the impact of primary PDAC CAFs on macrophage reprogramming in a folfirinox-dependent manner and performed various cellular assays (viability, immunophenotyping, phagocytosis, secretory profile analysis) and transcriptomic analysis.
2024-01-10 | GSE226448 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer associated fibroblasts (CAFs). CAFs promote tumor growth, metastasis and treatment resistance. We aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAFs) were generated by continuous incubation in 100nM gemcitabine. Gene expression differences between treatment naïve CAFs (N-CAFs) and R-CAFs were compared by array analysis. Immortalized human pancreatic CAFs were grown for 30 days in either control media or media containing 100nM gemcitabine. RNA was then isolated and hybidized on U133 Plus 2.0 Affymetrix arrays.
2016-03-09 | E-GEOD-78982 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma is an extreme lethal cancer with a poor treatment response to all the current chemotherapies. We generated a library of PDAC organoid lines from resected tumors, five from treatment-naive patients and five from patients who received neoadjuvant FOLFIRINOX (eight cycles). We assessed weather residual cancer cells in the tumor lesions of the patients treated with neoadjuvant FOLFIRINOX developed resistance to the treatment. Further we perfromed transcriptome analysis to investigate: 1- weather organoids recapitualting their corresponding tumor tissue 2- To investigate any modifications in the expression of the genes inflicted by FOLFIRINOX treatment.
2021-03-23 | GSE169321 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer associated fibroblasts (CAFs). CAFs promote tumor growth, metastasis and treatment resistance. We aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAFs) were generated by continuous incubation in 100nM gemcitabine. Gene expression differences between treatment naïve CAFs (N-CAFs) and R-CAFs were compared by array analysis.
2016-03-09 | GSE78982 | GEO
Project description:Gene expression in low passage pancreatic Cancer-associated Fibroblasts (CAFs) was assayed via Affymetrix HG U133plus2.0 arrays We used these array data to extract GPCR expression in human pancreatic CAFs, to compare with the same from RNA-seq and Taqman GPCR arrays
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Project description:Perineural invasion (PNI) is a unique biological feature of pancreatic cancer and is a key cause of pancreatic cancer metastasis, recurrence and poor postoperative survival, but its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) are closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles played an extremely important role in PNI in a dorsal root ganglion (DRG) coculture model and sciatic nerve model. To explore the lncRNA packaged in CAFs EVs, we conducted the lncRNA profile of CAFs isolated from pancreatic cancer
2024-04-20 | GSE264223 | GEO
Project description:While of growing interest in pancreatic cancer (PC) field, the stromal-tumor cells crosstalk lags behind in terms of biomarkers and therapeutic options improving the clinical armamentarium. Knowledge on cellular communications was drastically enhanced following the discovery of extracellular vesicles (EVs), a powerful process of intercellular exchanges. We previously described a new stromal-tumor cell crosstalk mediated by Cancer-Associated Fibroblasts (CAFs)-derived ANXA6+-EVs, supporting pancreatic cancer cell aggressiveness in hostile areas of PC. In this study, using mass spectrometry analyses to investigate CAFs-derived EVs' cargo, we report that CD9 is a key member of the ANXA6/LRP1/TSP1 complex present in PC-associated CAFs-derived ANXA6+-EVs. We determined that CD9 is expressed by PC-associated CAFs in vivo as well as in vitro following physiopathologic culture conditions. Targeting CD9 impaired CAFs-derived ANXA6+-EVs uptake by pancreatic cancer cells, which consequently decreases their migratory abilities. Signaling pathway arrays highlighted p38/MAPK as activated in pancreatic cancer cells following CAFs-derived ANXA6+/CD9+-EVs uptake. The use of CD9 blocking antibody, p38 siRNA or chemical inhibitors impaired pancreatic cancer cells abilities following incubation with CAFs-derived ANXA6+/CD9+-EVs. Finally, we revealed CD9 expression as an independent poor-prognosis marker in human PC samples. Collectively our data highlight the key role of CD9 in CAFs-derived ANXA6+-EVs internalization by pancreatic cancer cells and the consequent, and mandatory, activation of p38/MAPK pathway to foster their migratory abilities. Measuring the oncogenic CAFs-derived ANXA6+/CD9+-EVs then limiting their action on pancreatic cancer cells abilities might be a promising option for PC stratification and treatment.
2022-08-21 | PXD023165 | Pride
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer we used the DNA demethylating drug 5-aza-2’-deoxycytidine (DAC) in a KrasLSL-G12D; p53LSL-R270H/+; Pdx1-cre; Brca1flex2/flex2 (KPC-Brca1) mouse model of aggressive stroma-rich PDAC. In untreated tumors, we found globally decreased 5-methyl-cytosine (5mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAFs), and increased amounts of 5-hydroxymethyl-cytosine (5HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia (PanIN) to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the stromal CAFs. Expression profiling and immunohistochemistry highlighted DAC-induction of STAT1 in the tumors, and DAC plus gamma-interferon produced an additive anti-proliferative effect on PDAC cells. DAC induced strong expression of the testis antigen DAZL in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy. Treatment of a short-term explant culture of cancer-associated fibroblasts (CAFs) from a KPC-Brca1 mouse pancreatic carcinoma, with 2 micromolar 5-aza-dC (decitabine; DAC) for 48 hours. The experiment includes 3 replicate plates untreated and 3 replicates treated.
2013-01-01 | E-GEOD-42364 | biostudies-arrayexpress
Project description:Purpose: FOLFIRINOX has become standard therapy for patients with advanced stages pancreatic ductal adenocarcinoma (PDAC). However, only a subset of patients benefits from this therapy and biomarkers to guide clinical decisions are lacking. This study aimed to discover circulating microRNAs (miRNAs) as potential stratifying and monitoring biomarkers in patients with PDAC treated with FOLFIRINOX and to investigate their functional roles. Methods: A microarray was used in plasma samples from a first cohort of 11 patients selected based on their long versus short progression-free survival (PFS) after FOLFIRINOX. Nine miRNAs were validated using RT-qPCR in an independent cohort (n=43). The best discriminative miRNA was evaluated in tumor tissue samples and associated with clinicopathological features by Cox regression analyses. In vitro studies explored its role on cell proliferation, key downstream targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. Results: MiR-181a-5p was validated as significantly down-regulated in non-progressive compared to progressive patients after FOLFIRINOX. In multivariate analysis, this down-regulation correlated with improved PFS and overall survival, especially combined with CA19.9 decline (log-rank p<0.001, HR=0.153, 95% C.I. 0.067–0.347 and log-rank p=0.033, HR=0.201, 95% C.I. 0.070–0.576, respectively). Overexpression of miR-181a-5p increased proliferation of PDAC cells and inversely correlated with expression of ATM. Furthermore, inhibition of miR-181a-5p coupled with oxaliplatin exposure increased DNA damage and decreased cell viability. Conclusion: Our findings endorse miR-181a-5p as a biomarker for monitoring response to FOLFIRINOX and prognostication. MiR-181a-5p inhibition can potentially enhance sensitivity to oxaliplatin by amplifying the DNA damage response and cell death.
2019-01-01 | GSE109647 | GEO
Project description:We extracted primary CAFs from the tumor tissue of chemoresistant and chemosensitive pancreatic cancer patients (namely CAFR and CAFS). The Goal of this study is to compare the transcriptomes difference between CAFR and CAFS. And we come to a conclusion that CAFR is possessed of a iCAF phenotype.
2022-01-06 | GSE192907 | GEO