IL-8, a novel messenger to cross-link inflammation and tumor EMT via autocrine and paracrine pathways (Review)

Long, Xin-Xin; Ye, Yingnan; Zhang, Lijie; Liu, Pengpeng; Yu, Wenwen; Wei, Feng; Ren, Xiubao; Yu, Jinpu

doi:10.3892/ijo.2015.3234

Cited by 127 publications

(99 citation statements)

References 86 publications

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“…The same study provided evidence for different macrophage phenotype percentages in the tumours of CC and WSC patients . Our present findings point out to higher expression (as compared with WSC) of inflammatory factors in the serum and tumour of cachectic patients, for example, IL‐8, IFN‐α, GM‐CSF, EGF, VEGF, and G‐CSF, all of which have been reported to contribute to important molecular processes including angiogenesis, inflammation, tumour malignancy, and immune evasion IL‐8 has been described to be important marker in cachexia development …”

Section: Discussionsupporting

confidence: 75%

“…High expression of IL‐8 and VEGF is associated with induction of angiogenesis and progression of prostate cancer, ovarian cancer, and melanoma, and thus, these factors have been recently proposed as novel players in inflammation and tumour fibrosis . In addition, Chen et al .…”

Section: Discussionmentioning

confidence: 99%

“…42 High expression of IL-8 and VEGF is associated with induction of angiogenesis 50 and progression of prostate cancer, 48 ovarian cancer, 49 and melanoma, 51 and thus, these factors have been recently proposed as novel players in inflammation and tumour fibrosis. 47 In addition, Chen et al 52 described that the GM-CSF acts directly in epithelialmesenchymal transitions (EMT) by inducing MAPK activation in a murine colon cancer cell line. Unfortunately, the process of epithelial-mesenchymal transition and fibrosis in tumour micro-environment of cachectic patients remains unclear, as well as the contribution of this process for the development of the cachexia.…”

Section: Discussionmentioning

confidence: 99%

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Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

Lima

Simoes

Castro

et al. 2019

J cachexia sarcopenia muscle

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Background Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro‐environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro‐environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients. Methods 74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components. Results Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte–macrophage colony‐stimulating factor, interferon‐α, and interleukin (IL)‐8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight‐stable counterparts. Also, IL‐8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of α‐smooth muscle actin (P < 0.0001) in tumours of cachectic cancer patients, characterizing fibrosis. In addition, higher transforming growth factor (TGF)‐β1, TGF‐β2, and TGF‐β3 expression (P = 0.003, P = 0.05, and P = 0.047, respectively) was found in the tumour of cachectic patients, parallel to p38 mitogen‐activated protein kinase alteration. Hypoxia‐inducible factor‐1α mRNA content was significantly increased in the tumour of cachectic patients, when compared with weight‐stable group (P = 0.005). Conclusions Our results demonstrate TGF‐β pathway activation in the tumour in cachexia, through the (non‐canonical) mitogen‐activated protein kinase pathway. The results show that during cachexia, intratumoural inflammatory response contributes to the onset of fibrosis. Tumour remodelling, probably by TGF‐β‐induced transdifferentiation of fibroblasts to myofibroblasts, induces unbalanced inflammatory cytokine profile, angiogenesis, and elevation of extracellular matrix components (EMC). We speculate that these changes may affect tumour aggressiveness and present consequences in peripheral organs.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

Lima

Simoes

Castro

et al. 2019

J cachexia sarcopenia muscle

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“…Altogether, the data linking IL‐8 and EMT have established the principle of a mutual loop in which IL‐8 and EMT programs sustain each other in the cancer microenvironment (Long et al ., ).…”

Section: Emt and Soluble Factors Of Inflammationmentioning

confidence: 97%

EMT and inflammation: inseparable actors of cancer progression

et al. 2017

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Tumors can be depicted as wounds that never heal, and are infiltrated by a large array of inflammatory and immune cells. Tumor‐associated chronic inflammation is a hallmark of cancer that fosters progression to a metastatic stage, as has been extensively reviewed lately. Indeed, inflammatory cells persisting in the tumor establish a cross‐talk with tumor cells that may result in a phenotype switch into tumor‐supporting cells. This has been particularly well described for macrophages and is referred to as tumor‐associated ‘M2’ polarization. Epithelial‐to‐mesenchymal transition (EMT), the embryonic program that loosens cell–cell adherence complexes and endows cells with enhanced migratory and invasive properties, can be co‐opted by cancer cells during metastatic progression. Cancer cells that have undergone EMT are more aggressive, displaying increased invasiveness, stem‐like features, and resistance to apoptosis. EMT programs can also stimulate the production of proinflammatory factors by cancer cells. Conversely, inflammation is a potent inducer of EMT in tumors. Therefore, the two phenomena may sustain each other, in an alliance for metastasis. This is the focus of this review, where the interconnections between EMT programs and cellular and molecular actors of inflammation are described. We also recapitulate data linking the EMT/inflammation axis to metastasis.

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“…CXCL8 is upregulated in many cancers including solid tumors (brain, breast, colon, gastric, lung, and others) and blood cancers (AML, CLL, Hodgkin’s lymphoma) and high levels of CXCL8 expression are often linked with disease progression 13 . CXCL8 can function in both a paracrine manner to alter the immune composition of the TME as well as in an autocrine manner to regulate tumor cell EMT and invasion 14 . The role of CXCL8 and its homologs in recruiting neutrophils to established tumors has been demonstrated in various Ras-driven cancer models 15,16 , however its role in recruiting neutrophils to tumor-initiating cells and the role of specific receptors is unclear.…”

Section: Introductionmentioning

confidence: 99%

Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo

Powell

Meng

Barros-Becker

et al. 2018

Sci Rep

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Neutrophils are first-responders to sites of infection and tissue damage including the inflamed tumor microenvironment. Increasing evidence suggests that crosstalk between tumors and neutrophils can affect the progression of established tumors. However, there is a gap in our understanding of the early events that lead to neutrophil recruitment to oncogene-transformed cells and how these pathways alter tumor progression. Here, we use optically transparent zebrafish larvae to probe the early signals that mediate neutrophil recruitment to Kras-transformed astrocytes. We show that zebrafish larvae with impaired neutrophil function exhibit reduced proliferation of transformed astrocytes supporting a critical role for tumor-associated neutrophils in the early progression of tumorigenesis. Moreover, using mutants and pharmacological inhibition, we show that the chemokine receptor Cxcr1 promotes neutrophil recruitment, proliferation of tumor-initiating cells, and neoplastic mass formation. These findings highlight the power of the larval zebrafish system to image and probe early events in the tumor-initiating microenvironment and demonstrate the potential for neutrophil recruitment signaling pathways such as Cxcl8-Cxcr1 as targets for anti-cancer therapies.

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IL-8, a novel messenger to cross-link inflammation and tumor EMT via autocrine and paracrine pathways (Review)

Cited by 127 publications

References 86 publications

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

EMT and inflammation: inseparable actors of cancer progression

Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo

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