Acquisition of gemcitabine resistance enhances angiogenesis via upregulation of IL‑8 production in pancreatic cancer

Imafuji, Hiroyuki; Matsuo, Yoichi; Ueda, Gaiko; Omi, Kan; Hayashi, Yuichi; Saito, Kenta; Tsuboi, Koji; Morimoto, Mamoru; Koide, Shuji; Ogawa, Ryo; Hara, Masayasu; Takahashi, Hiroki; Takiguchi, Shuji

doi:10.3892/or.2019.7105

Cited by 11 publications

(16 citation statements)

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“…CXCR2 significantly promotes angiogenesis, proliferation, and invasion of pancreatic cancer [ 139 ]. Pancreatic cancer cell increases CXCL8 secretion to enhance angiogenesis and acquisition of gemcitabine resistance [ 140 ]. CXCR1 promotes proliferation, migration, invasion, and metastasis in gastric cancer in vitro and in vivo [ 141 ].…”

Section: Cxcl8-cxcr1/2 Signaling Pathwaymentioning

confidence: 99%

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Han

Yang

et al. 2021

Molecules

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In humans, Interleukin-8 (IL-8 or CXCL8) is a granulocytic chemokine with multiple roles within the tumor microenvironment (TME), such as recruiting immunosuppressive cells to the tumor, increasing tumor angiogenesis, and promoting epithelial-to-mesenchymal transition (EMT). All of these effects of CXCL8 on individual cell types can result in cascading alterations to the TME. The changes in the TME components such as the cancer-associated fibroblasts (CAFs), the immune cells, the extracellular matrix, the blood vessels, or the lymphatic vessels further influence tumor progression and therapeutic resistance. Emerging roles of the microbiome in tumorigenesis or tumor progression revealed the intricate interactions between inflammatory response, dysbiosis, metabolites, CXCL8, immune cells, and the TME. Studies have shown that CXCL8 directly contributes to TME remodeling, cancer plasticity, and the development of resistance to both chemotherapy and immunotherapy. Further, clinical data demonstrate that CXCL8 could be an easily measurable prognostic biomarker in patients receiving immune checkpoint inhibitors. The blockade of the CXCL8-CXCR1/2 axis alone or in combination with other immunotherapy will be a promising strategy to improve antitumor efficacy. Herein, we review recent advances focusing on identifying the mechanisms between TME components and the CXCL8-CXCR1/2 axis for novel immunotherapy strategies.

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Section: Cxcl8-cxcr1/2 Signaling Pathwaymentioning

confidence: 99%

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Han

Yang

et al. 2021

Molecules

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“…VEGF-alpha, an angiogenesis regulator, is expressed in approximately 50% of iCCA tumors and is associated with increased microvascular density and poor prognosis [41][42][43]. Studies on IL-6 and IL-8 show that they play important roles in protecting pancreatic adenocarcinoma from gemcitabine-induced apoptosis [44,45]. In response to CAFs, miR-206 expression was further downregulated in CCA cells.…”

Section: Discussionmentioning

confidence: 99%

MiR-206 suppresses the deterioration of intrahepatic cholangiocarcinoma and promotes sensitivity to chemotherapy by inhibiting interactions with stromal CAFs

Yang¹,

Wang²,

Han³

et al. 2022

Int. J. Biol. Sci.

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“…Many solid tumors show high levels of IL-8, a fibro-inflammatory cytokine, which promotes angiogenesis, tumor cell proliferation, metastasis and drug resistance [52][53][54]. Targeting IL-8 has been proposed as a treatment for several cancers including breast cancer [55,56], pancreatic [57], and pre-leukemic stem cells [58]. In patients with chronic obstructive pulmonary disease, IL-8 levels can be diagnostic of lung cancer [59] and serum IL-8 levels are correlative with lung cancer risk [60].…”

Section: Discussionmentioning

confidence: 99%

Role of TLR4 Receptor Complex in the Regulation of the Innate Immune Response by Fibronectin

Zheng

Ambesi

McKeown‐Longo

2020

Cells

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Chronic inflammation and subsequent tissue fibrosis are associated with a biochemical and mechanical remodeling of the fibronectin matrix. Due to its conformational lability, fibronectin is considerably stretched by the contractile forces of the fibrotic microenvironment, resulting in the unfolding of its Type III domains. In earlier studies, we have shown that a peptide mimetic of a partially unfolded fibronectin Type III domain, FnIII-1c, functions as a Damage Associated Molecular Pattern (DAMP) molecule to induce activation of a toll-like receptor 4 (TLR4)/NF-κB pathway and the subsequent release of fibro-inflammatory cytokines from human dermal fibroblasts. In the current study, we evaluated the requirement of the canonical TLR4/MD2/CD14 receptor complex in the regulation of FnIII-1c induced cytokine release. Using dermal fibroblasts and human embryonic kidney (HEK) cells, we found that all the components of the TLR4/MD2/CD14 complex were required for the release of the fibro-inflammatory cytokine, interleukin 8 (IL-8) in response to both FnIII-1c and the canonical TLR4 ligand, lipopolysaccharide (LPS). However, FnIII-1c mediated IL-8 release was strictly dependent on membrane-associated CD14, while LPS could use soluble CD14. These findings demonstrate that LPS and FnIII-1c share a similar but not identical mechanism of TLR4 activation in human dermal fibroblasts.

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Acquisition of gemcitabine resistance enhances angiogenesis via upregulation of IL‑8 production in pancreatic cancer

Cited by 11 publications

References 0 publications

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy

MiR-206 suppresses the deterioration of intrahepatic cholangiocarcinoma and promotes sensitivity to chemotherapy by inhibiting interactions with stromal CAFs

Role of TLR4 Receptor Complex in the Regulation of the Innate Immune Response by Fibronectin

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