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Series GSE164088 Query DataSets for GSE164088
Status Public on Jun 05, 2021
Title Gene expression profile of primary CAFs exposed to PARPi or not derived from ovarian cancer patients
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Cancer-associated fibroblasts (CAFs) play significant roles in drug resistance through different ways. Antitumor therapies, including molecular targeted interventions, not only effect tumor cells but also modulate the phenotype and characteristics of CAFs, which can in turn blunt the therapeutic response. Little is known about how stromal fibroblasts respond to poly (ADP-ribose) polymerase
inhibitors (PARPis) in ovarian cancer (OC) and subsequent effects on tumor cells. This is a study to evaluate how CAFs react to PARPis and their potential influence on PARPi resistance in OC. We discovered that OC stromal fibroblasts exhibited intrinsic resistance to PARPis and were further activated after the administration of PARPis. PARPi-challenged fibroblasts displayed a specific secretory profile characterized by increased secretion of CCL5, MIP-3α, MCP3, CCL11, and ENA-78. Mechanistically, increased secretion of CCL5 through activation of the NF-κB signaling pathway was required for PARPi-induced stromal fibroblast activation in
an autocrine manner. Moreover, neutralizing CCL5 partly reversed PARPi-induced fibroblast activation and boosted the tumor inhibitory effect of PARPis in both BRCA1/2-mutant and BRCA1/2-wild type xenograft models. Our study revealed that PARPis could maintain and improve stromal fibroblast activation involving CCL5 autocrine upregulation. Targeting CCL5 might offer a new treatment modality in overcoming the reality of PARPi resistance in OC.
Overall design Three strains of primary CAFs were isolated. Each strain of CAF was amplified in nine T75 culture flasks, when the confluence reached 60-70%, one was exposed to DMSO as control, the next one was exposed to 30uM olaparib and another one was exposed to 20uM niraparib; each kind of treatment was conducted in triplicate. After 72 hours, cells from each culture flask were gathered and dissoved in 1ml Trizol and stored in -80℃ for RNA-seq.
Contributor(s) Li X, Fang T, Yang Z, Gao Q
Citation(s) 34108603
Submission date Dec 31, 2020
Last update date Jun 15, 2021
Contact name Tian Fang
Organization name Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Lab Cancer Biology Research Center, Key Laboratory of the Ministry of Education
Street address Jiefang Avenue
City Wuhan
State/province Hubei
ZIP/Postal code 430030
Country China
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (18)
GSM4996442 CAF1-CON1
GSM4996443 CAF1-CON2
GSM4996444 CAF1-CON3
BioProject PRJNA688884
SRA SRP299896

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Supplementary file Size Download File type/resource
GSE164088_fpkm.ann.xls.xlsx 7.9 Mb (ftp)(http) XLSX
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Processed data are available on Series record

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