The potential of CXCL5 as a target for liver cancer – what do we know so far?

Xia, Jinglin; Xu, Xiaojing; Huang, Peixin; He, Min; Wang, Xiangdong

doi:10.1517/14728222.2014.993317

Cited by 22 publications

(20 citation statements)

References 23 publications

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“…However, the preponderance of evidence showed that chemokines contribute mainly to carcinogenesis in the progress of cancers (19). Although CXCL5 has been reported to have numerous roles in carcinomas (20,21), to the best of our knowledge, the present study was the first to conduct a paracrine secretion assay to investigate the effects of endogenous CXCL5 secreted by hepatic stellate LX-2 cells on the oncogenic potential of HB HepG2 cells. HepG2 was originally thought to be a hepatocellular carcinoma cell line and was utilized to investigate hepatocellular carcinoma.…”

Section: Discussionmentioning

confidence: 91%

CXCL5 as an autocrine or paracrine cytokine is associated with proliferation and migration of hepatoblastoma HepG2 cells

et al. 2017

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Abstract. C-X-C motif chemokine ligand 5 (CXCL5) is a CXC-type chemokine that is a crucial inflammatory mediator and a powerful attractant for granulocytic immune cells. Increasing evidence has indicated that CXCL5 is involved in the tumorigenesis of various malignancies. The present investigation demonstrated that CXCL5 was expressed in both hepatoblastoma HepG2 cells and liver stellate LX-2 cells, and CXCL5's receptor C-X-C chemokine receptor type 2 (CXCR2) was expressed in HepG2 cells by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and ELISA assays. Cell counting kit-8, colony formation and Transwell assays revealed that exogenous CXCL5 expression efficiently promoted proliferation, colony formation and migration of HepG2 cells. To explore the autocrine and paracrine roles of CXCL5 in the oncogenic potential of HepG2 cells, HepG2 cells overexpressing CXCL5 and LX-2 cells overexpressing CXCL5 were successfully constructed by gene transfection. Similarly, overexpression of CXCL5 in HepG2 also enhanced proliferation, colony formation and migration of HepG2 cells. Furthermore, the condition medium of LX-2 cells overexpressing CXCL5 affected the proliferation and migration of HepG2 cells. RT-PCR and western blotting assays were also conducted to explore whether overexpression of CXCL5 in HepG2 modulated the expression of genes. The results revealed that overexpression of CXCL5 regulated the expression of several genes, including N-myc downregulated gene 3,w B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, P53, vascular endothelial growth factor, interleukin (IL)-18, IL-1β and cystathionine-γ-lyase. In conclusion, the present findings indicate that CXCL5/CXCR2 axis contributes to the oncogenic potential of hepatoblastoma via autocrine or paracrine pathways by regulating expression of genes associated with the progression of carcinoma. IntroductionHepatoblastoma (HB) is a prevalent malignancy among children, which histologically derives from pluripotent stem cells that may differentiate into liver cells and biliary epithelial cells, and accounts for almost two-thirds of pediatric malignant liver tumors (1,2). Although the survival rate of HB has increased from 35 to 75% during the last 30 years with the application of surgical excision, adjuvant chemotherapy and liver transplantation (3), additional investigation of the underlying molecular mechanism will be beneficial for the improving diagnosis and treatment of patients with HB.Previous studies have supported the hypothesis that the development of malignancies is closely associated with various cytokines, in which chemokines appear to have crucial roles. Chemokines are members of the cytokine super family and are secreted by various cell types, including immune, mesothelial, endometrial glandular and stromal cells, and trophoblasts (4). According to the order of conserved cysteine residues, chemokines are classified as C, CC, CXC and C (X) 3 C. Additionally, CXC chemokines are further grouped into ELR + CXC and ELR -CXC on the b...

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Section: Discussionmentioning

confidence: 91%

CXCL5 as an autocrine or paracrine cytokine is associated with proliferation and migration of hepatoblastoma HepG2 cells

et al. 2017

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“…Nonetheless, since our analyses focused on CAFs derived from tumor tissues, which were observed to express CXCL5 significantly, we suggest that the expression of CXCL5 may be the character rather than the symbol of CAFs in melanoma and CRC. In liver cancer, CXCL5 was reported to be a candidate of diagnostic and therapeutic biomarkers with potential clinical values . Meanwhile, CXCL5 could also attract neutrophil toward melanoma and HCC .…”

Section: Discussionmentioning

confidence: 99%

“…In liver cancer, CXCL5 was reported to be a candidate of diagnostic and therapeutic biomarkers with potential clinical values. 29 Meanwhile, CXCL5 could also attract neutrophil toward melanoma and HCC. 25,30 Therefore, CXCL5 affects the complex tumor microenvironment at multiple ways.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Zhou

Zhang

et al. 2019

Intl Journal of Cancer

153

131

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Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating the tumor malignant biological properties within tumor microenvironment and evidences demonstrate that CAFs are a critical regulator of tumoral immunosuppression of the T cell response. However, the functions and regulation of CAFs in the expression of programmed death‐ligand 1 (PD‐L1) in melanoma and colorectal carcinoma (CRC) are not completely understood. Herein, by scrutinizing the expression of α‐SMA and PD‐L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD‐L1 expression. Further analyses showed that CAFs promoted PD‐L1 expression in mice tumor cells. By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. In addition, CXCL5 promoted PD‐L1 expression in B16, CT26, A375 and HCT116. The silencing of CXCR2, the receptor of CXCL5, inhibited the PD‐L1 expression induced by CAFs in turn. Functionally, CXCL5 derived by CAFs promoted PD‐L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD‐L1 expression via PI3K/AKT signaling. Meanwhile, the B16/CT26 xenograft tumor models were used and both CXCR2 and p‐AKT were found to be positively correlated with PD‐L1 in the xenograft tumor tissues. The immunosuppressive action of CAFs on tumor cells is probably reflective of them being a potential therapeutic biomarker for melanoma and CRC.

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“…CXCL5 belongs to the CXC chemokine family, has specificity for CXCR2 receptors, and is involved in the recruitment and activation of neutrophils [65]. CXCL5 is associated with neutrophil infiltration and poor prognosis in liver cancer, and is considered a therapeutic target in liver cancer, as treatment with small-interfering RNAs or antibodies against CXCL5 can suppress tumor growth, proliferation, migration and invasion [66]. In non-small cell lung cancer cells, CXCL5 was identified as a downstream target of MALAT1 , and together, they regulated cell migration and invasion [67].…”

Section: Discussionmentioning

confidence: 99%

Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells

Leti

Legendre

Still

et al. 2017

Translational Research

100

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In the present study, we sought to identify lncRNA expression profiles in NASH patients with histological evidence of lobular inflammation and advanced fibrosis. We profiled lncRNA expression using RNA-sequencing of wedge liver biopsies from 24 NAFLD patients with normal liver histology, 53 NAFLD patients with lobular inflammation, and 65 NAFLD patients with advanced fibrosis. Transcript profiling identified 4432 and 4057 differentially expressed lncRNAs in comparisons of normal tissue with lobular inflammation and fibrosis samples, respectively. Functional enrichment analysis revealed lncRNA participation in TGFB1 and TNF signaling, insulin resistance, and extracellular matrix maintenance. Several lncRNAs were highly expressed in fibrosis relative to normal tissue, including nuclear paraspeckle assembly transcript 1 (NEAT1), hepatocellular carcinoma upregulated lncRNA (HULC), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Two potential target mRNAs, syndecan 4 (SDC4) and C-X-C motif chemokine ligand 5 (CXCL5) were identified for HULC and MALAT1, respectively, but only CXCL5 showed differential expression among the different histological classes. Knockdown of MALAT1 expression reduced CXCL5 transcript and protein levels by 50% and 30%, respectively, in HepG2 cells. Expression of MALAT1 and CXCL5 was upregulated in activated hepatic stellate (LX-2) cells compared to cells in the quiescent state, and MALAT1 expression was regulated by hyperglycemia and insulin in HepG2 cells, but only by insulin in LX-2 cells. Dysregulated lncRNA expression is associated with inflammation and fibrosis in NASH. Functionally relevant differences in MALAT1 expression may contribute to the development of fibrosis in NASH through mechanisms involving inflammatory chemokines.

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The potential of CXCL5 as a target for liver cancer – what do we know so far?

Cited by 22 publications

References 23 publications

CXCL5 as an autocrine or paracrine cytokine is associated with proliferation and migration of hepatoblastoma HepG2 cells

CXCL5 as an autocrine or paracrine cytokine is associated with proliferation and migration of hepatoblastoma HepG2 cells

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells

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