CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression

Su, Shan; Sun, Xueqin; Zhang, Qinghua; Zhang, Zhe; Chen, Ju

doi:10.1247/csf.18029

Cited by 15 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vasoactive Intestinal Peptide, encoded by VIP, is known to be involved in autocrine as well as paracrine signaling loop that promotes cancer growth in multiple cancer types [32]. CCL20 gene encodes the chemokine C-C Motif Chemokine Ligand 20 and it was identified to play a role in metastasis and therapy resistance of ovarian cancer cells [33,34].…”

Section: Discussionmentioning

confidence: 99%

GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer

Jayaraman

Yan

et al. 2021

Biomolecules

View full text Add to dashboard Cite

Increased expression of GNAi2, which encodes the α-subunit of G-protein i2, has been correlated with the late-stage progression of ovarian cancer. GNAi2, also referred to as the proto-oncogene gip2, transduces signals from lysophosphatidic acid (LPA)-activated LPA-receptors to oncogenic cellular responses in ovarian cancer cells. To identify the oncogenic program activated by gip2, we carried out micro-array-based transcriptomic and bioinformatic analyses using the ovarian cancer cell-line SKOV3, in which the expression of GNAi2/gip2 was silenced by specific shRNA. A cut-off value of 5-fold change in gene expression (p < 0.05) indicated that a total of 264 genes were dependent upon gip2-expression with 136 genes coding for functional proteins. Functional annotation of the transcriptome indicated the hitherto unknown role of gip2 in stimulating the expression of oncogenic/growth-promoting genes such as KDR/VEGFR2, CCL20, and VIP. The array results were further validated in a panel of High-Grade Serous Ovarian Carcinoma (HGSOC) cell lines that included Kuramochi, OVCAR3, and OVCAR8 cells. Gene set enrichment analyses using DAVID, STRING, and Cytoscape applications indicated the potential role of the gip2-stimulated transcriptomic network involved in the upregulation of cell proliferation, adhesion, migration, cellular metabolism, and therapy resistance. The results unravel a multi-modular network in which the hub and bottleneck nodes are defined by ACKR3/CXCR7, IL6, VEGFA, CYCS, COX5B, UQCRC1, UQCRFS1, and FYN. The identification of these genes as the critical nodes in GNAi2/gip2 orchestrated onco-transcriptome establishes their role in ovarian cancer pathophysiology. In addition, these results also point to these nodes as potential targets for novel therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer

Jayaraman

Yan

et al. 2021

Biomolecules

View full text Add to dashboard Cite

show abstract

“…CCL20 levels are elevated in many cancer types such as breast, liver, and pancreatic cancers, but are low in adrenal gland and lung cancers (31). In OC, it has been reported to contribute to promoting chemotherapy resistance, stimulating migration, and poor disease prognosis (35)(36)(37). Increased CCL20 levels were found in serum samples from patients with recurrent OC who were completely treated with platinum-based chemotherapy and correlated with decreased recurrence-free survival rates (19).…”

Section: S1amentioning

confidence: 99%

Accuracy of CCL20 expression level as a liquid biopsy-based diagnostic biomarker for ovarian carcinoma

Sakares

Wongkhattiya²,

Vichayachaipat³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

ObjectiveThe study aimed to investigate the potentiality of chemokines, including MCP-1, CCL15, CCL20, and CXCL14, as biomarkers for differential diagnosis between benign tumors and ovarian cancer (OC).MethodsA cross-sectional study was conducted in women aged >18 years who had adnexal masses treated with elective surgery at the HRH Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, between 2020 and 2021. The preoperative MCP-1, CCL15, CCL20, and CXCL14 serum levels were measured using a sandwich enzyme-linked immunosorbent assay. Preoperative diagnosis was defined according to the risk of malignancy index. The histological diagnosis and cancer subtype were confirmed using pathological specimens.ResultsNinety-eight participants were preoperatively diagnosed with malignant tumors. The pathological diagnosis confirmed OC in 33 patients and disclosed 27 misdiagnosed cases, of which endometriotic cyst was the most common (44.44%). CCL20 and CA125 serum levels were significantly higher in the patients with cancer than in those with benign. In addition, CCL20 level could differentiate between benign and early-stage malignancy. Furthermore, only CCL20 levels could distinguish endometriotic cysts from OC, whereas CA125 levels could not. Concordant with the serum protein level, the increased mRNA level of CCL20 was observed in ovarian cancers comparing with that in benign tissues. We found that CCL20 levels could differentiate between benign tumors and OC with 60.61% sensitivity and 75.44% specificity at the optimal cutoff value of 38.79 pg/ml. Finally, the logistic regression model integrating CCL20, CA125, and menopause status promoted diagnostic accuracy by increasing the specificity to 91.23%.ConclusionsOur study revealed the potential usefulness of CCL20 level as a biomarker for diagnosing early-stage OC with endometriosis differentiation. We recommend further studies to confirm the accuracy of CCL20 levels with the current diagnosis in a large patient sample.

show abstract

“…In addition, stroma-derived CCL2 and CCL5 induce tumor cells to release IL-6 by activating the PYK2 signaling pathway (located upstream of the JAK1/STAT3 signaling pathway), thereby resulting in carboplatin resistance (72). Similarly, the regulation of CCL20 expression via ATP-binding cassette subfamily B member 1 membrane transporter is associated with doxorubicin resistance (73). Vaquero et al (74) examined 109 genes that may be associated with chemotherapeutic drug resistance in HCC and found that CCL14 and CCL15 mRNA expression was upregulated following activation of nuclear receptor FXR; this upregulation was involved in drug resistance and the mechanism of chemoresistance (MOC) may be associated with changes in the balance of apoptosis-promoting (MOC-5a) and survival-promoting (MOC-5b) genes.…”

Section: CCmentioning

confidence: 99%

Role of chemokines in hepatocellular carcinoma (Review)

et al. 2020

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges for the treatment of HCC is the prevention or management of recurrence and metastasis of HCC. It has been found that chemokines and their receptors serve a pivotal role in HCC progression. In the present review, the literature on the multifactorial roles of exosomes in HCC from PubMed, Cochrane library and Embase were obtained, with a specific focus on the functions and mechanisms of chemokines in HCC. To date, >50 chemokines have been found, which can be divided into four families: CXC, CX3C, CC and XC, according to the different positions of the conserved N-terminal cysteine residues. Chemokines are involved in the inflammatory response, tumor immune response, proliferation, invasion and metastasis via modulation of various signaling pathways. Thus, chemokines and their receptors directly or indirectly shape the tumor cell microenvironment, and regulate the biological behavior of the tumor. In addition, the potential application of chemokines in chemotaxis of exosomes as drug vehicles is discussed. Exosomes containing chemokines or expressing receptors for chemokines may improve chemotaxis to HCC and may thus be exploited for targeted drug delivery.

show abstract

CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression

Cited by 15 publications

References 29 publications

GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer

GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer

Accuracy of CCL20 expression level as a liquid biopsy-based diagnostic biomarker for ovarian carcinoma

Role of chemokines in hepatocellular carcinoma (Review)

Contact Info

Product

Resources

About