IL‑8 is upregulated in cervical cancer tissues and is associated with the proliferation and migration of HeLa cervical cancer cells

Liu, Jia; Li, Fengying; Shao, Mingliang; Zhang, Wei; Zhang, Chunbin; Zhao, Xiao-Lian; Luan, Hemi; Qi, Yaling; Zhang, Pengxia; Liang, Lichun; Jia, Xiuyue; Zhang, Kun; Lü, Yan; Yang, Zhe; Zhu, Xiulin; Zhang, Qi; Du, Juan; Wang, Weiqun

doi:10.3892/ol.2017.7391

Cited by 19 publications

(18 citation statements)

References 37 publications

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“…IL-33 promotes cellular proliferation and invasion in ovarian cancer by activating ERK1/2, as demonstrated by the complete abrogation of these responses in cells treated with the ERK inhibitor U0126 [52]. Moreover, ERKs mediate proliferation and/or migration in response to IL-8 in pancreatic [53] and cervical [54] cancer, to IL-34 in colon cancer cells [55], and to IL-13 in glioblastoma multiforme [56], working as downstream collectors of the pro-tumorigenic inputs of different cytokines.…”

Section: Erks Favor An Aggressive Phenotype In Tumors In Response mentioning

confidence: 99%

ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer

Salaroglio

Mungo

Gazzano

et al. 2019

IJMS

103

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The extracellular signal-related kinases (ERKs) act as pleiotropic molecules in tumors, where they activate pro-survival pathways leading to cell proliferation and migration, as well as modulate apoptosis, differentiation, and senescence. Given its central role as sensor of extracellular signals, ERK transduction system is widely exploited by cancer cells subjected to environmental stresses, such as chemotherapy and anti-tumor activity of the host immune system. Aggressive tumors have a tremendous ability to adapt and survive in stressing and unfavorable conditions. The simultaneous resistance to chemotherapy and immune system responses is common, and ERK signaling plays a key role in both types of resistance. In this review, we dissect the main ERK-dependent mechanisms and feedback circuitries that simultaneously determine chemoresistance and immune-resistance/immune-escape in cancer cells. We discuss the pros and cons of targeting ERK signaling to induce chemo-immune-sensitization in refractory tumors.

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Section: Erks Favor An Aggressive Phenotype In Tumors In Response mentioning

confidence: 99%

ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer

Salaroglio

Mungo

Gazzano

et al. 2019

IJMS

103

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“…This indicates that RANKL may stimulate cervical cancer growth by activation of the IL-8 pathway. Jia et al recently showed that the expression of IL-8 was significantly higher in cervical carcinoma samples compared to normal controls and that migration and proliferation of Hela cells increased after treatment with IL-8 [69]. Survival of cervical cancer patients with high intratumoral IL-8 expression is significantly worse compared to patients with low IL-8 in their tumors [70].…”

Section: Rank-mediated Signaling and Cervical Cancermentioning

confidence: 99%

RANK-RANKL Signaling in Cancer of the Uterine Cervix: A Review

Dam

Verhoeven

Jacobs

et al. 2019

IJMS

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RANK ligand (RANKL) is a member of the tumor necrosis factor alpha superfamily of cytokines. It is the only known ligand binding to a membrane receptor named receptor activator of nuclear factor-kappa B (RANK), thereby triggering recruitment of tumor necrosis factor (TNF) receptor associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor called osteoprotegerin (OPG), but also has additional more complex levels of regulation. The existing literature on RANK/RANKL signaling in cervical cancer was reviewed, particularly focusing on the effects on the microenvironment. RANKL and RANK are frequently co-expressed in cervical cancer cells lines and in carcinoma of the uterine cervix. RANKL and OPG expression strongly increases during cervical cancer progression. RANKL is directly secreted by cervical cancer cells, which may be a mechanism they use to create an immune suppressive environment. RANKL induces expression of multiple activating cytokines by dendritic cells. High RANK mRNA levels and high immunohistochemical OPG expression are significantly correlated with high clinical stage, tumor grade, presence of lymph node metastases, and poor overall survival. Inhibition of RANKL signaling has a direct effect on tumor cell proliferation and behavior, but also alters the microenvironment. Abundant circumstantial evidence suggests that RANKL inhibition may (partially) reverse an immunosuppressive status. The use of denosumab, a monoclonal antibody directed to RANKL, as an immunomodulatory strategy is an attractive concept which should be further explored in combination with immune therapy in patients with cervical cancer.

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“… 18 Multiple cervical cancer cell lines have been shown to synthesize and secrete IL-6/8 in vitro. 20 , 21 IL-6 and IL-8 are multifunctional cytokines that regulate inflammation and cancer development. 20 , 22 – 24 Increasing evidence demonstrates that IL-6/8 plays a vital role in the pathogenesis of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

FPR1 mediates the tumorigenicity of human cervical cancer cells

Cao¹,

Zhang²

2018

CMAR

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PurposeThe present study aimed to investigate the role of FPR1 and the downstream effectors such as NF-κB and IL-6/8 in the development of cervical cancer.Patients and methodsFPR1 protein expression was detected via immunohistochemical staining in tissue microarrays containing cervical cancer tissues from 185 patients. Following FPR1 silencing in SiHa cells using lentiviral siRNA delivery, biological characteristics and tumor formation were evaluated in vitro and in vivo, respectively. Phosphorylated NF-κB levels were detected by Western blotting, while IL-6 and IL-8 secretion were detected by ELISA in both FPR1 knockdown and control SiHa cells. Human umbilical vein endothelial cell tube formation assays were performed to evaluate the angiogenesis-promoting ability of IL-6 and IL-8 secretion in FPR1 knockdown and control SiHa cells. Neovascularization, proliferation and apoptosis markers were detected by immunohistochemical staining to analyze the tumorigenic role of FPR1.ResultsImmunohistochemistry of cervical cancer tissues from 185 patients revealed high FPR1 expression levels in patients with advanced-stage disease and/or poor prognosis. Compared with control cells, cervical cancer cells in which FPR1 was silenced exhibited inhibition of cell invasion, migration and proliferation and higher levels of apoptosis. NF-κB was inhibited in FPR1 knockdown in SiHa cells. IL-6/8 upregulation by FPR1 activation stimulated angiogenesis. FPR1 deficiency inhibited the tumorigenicity of cervical cancer cells in nude mice. FPR1, IL-6, IL-8, CD31 and Ki67 levels were all reduced, whereas cleaved caspase-3 was upregulated, in the FPR1 knockdown group compared with the levels in the control group.ConclusionHigh FPR1 expression was associated with advanced stage and poor prognosis in cervical cancer patients. FPR1 activation induced NF-κB nuclear translocation to promote cervical cancer development through the upregulation of IL-6 and IL-8 expression. Inhibiting FPR1 activity may thus have potential therapeutic value in cervical cancer patients.

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IL‑8 is upregulated in cervical cancer tissues and is associated with the proliferation and migration of HeLa cervical cancer cells

Cited by 19 publications

References 37 publications

ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer

ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer

RANK-RANKL Signaling in Cancer of the Uterine Cervix: A Review

FPR1 mediates the tumorigenicity of human cervical cancer cells

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