CXCL1 promotes tumor growth through VEGF pathway activation and is associated with inferior survival in gastric cancer

Wei, Zhe; Xia, Guang; Wu, Ying; Chen, Wei; Xiang, Zhen; Schwarz, Roderich E.; Brekken, Rolf A.; Awasthi, Niranjan; He, Yu; Zhang, Chang Hua

doi:10.1016/j.canlet.2015.01.033

Cited by 88 publications

(87 citation statements)

References 41 publications

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“…Through a range of signaling processes that stimulate the growth, migration, survival, and permeability of vascular endothelial cells, the VEGF pathway is able to trigger various functions, thereby activating the process of neovascularization by which endothelial cells arise from progenitor cells and new blood vessels sprout from old ones. The expression of VEGF mRNA has been reported to correlate with poor prognosis and liver metastasis in primary gastric cancer [10, 26, 36]. The results of ELISA in our experiment demonstrated that the level of secreted VEGF correlated with the liver metastasis potential of gastric cancer cell lines, with relatively higher levels of VEGF secreted by the highly metastatic liver cell line MKN45 compared with the low metastatic gastric cancer cell lines NUGC-4 and AGS.…”

Section: Discussionsupporting

confidence: 62%

Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer

Gong

et al. 2018

Int J Clin Oncol

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BackgroundInterleukin-1 alpha (IL-1α) plays an important role in tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the interactions of tumor cells and their micro-environment is poorly understood. We have evaluated the role of IL-1RA in the metastatic process as well as the mutual or reciprocal actions between gastric cancer cells and stromal cells.Materials and methodsThe expressions of IL-1α, vascular endothelial growth factor (VEGF), and IL-1RI mRNA were determined by reverse transcriptase-PCR. The regulatory effect of IL-1RA on the secretion of VEGF in human gastric cancer cells and human umbilical vein endothelial cells (HUVECs) was detected by enzyme-linked immunosorbent assay. The effect of IL-1RA on metastatic potential was evaluated using proliferation, invasion, and angiogenesis assays, respectively, including in vitro co-culture system models consisting of tumor cells and stromal cells that were used to detect invasion and angiogenesis.ResultsInterleukin-1α mRNA was detected in the higher liver metastatic gastric cell line MKN45. IL-1α protein was expressed in MKN45 cells and in HUVECs. VEGF mRNA and protein were detected in the three gastric cancer cell lines (MKN4, NUGC-4, and AGS). Levels of VEGF secreted by gastric cancer cells and HUVECs appeared to be reduced through the action of IL-1RA via IL-1RI in a dose-dependent manner (P < 0.01). IL-1RA significantly inhibited the proliferation and migration of HUVECs (P < 0.01) and tube formation by HUVECs (P < 0.01), both in a dose-dependent manner. Compared with HUVECs grown without cancer cells (control) or with NUGC-4 cells, tube formation by HUVECs was significantly enhanced by co-culture with MKN45 cells (P < 0.01). The enhanced tube formation in the presence of MKN45 cells was inhibited by the addition of IL-1RA (P < 0.01).ConclusionsThe IL-1RA downregulated the metastatic potential of gastric cancer through blockage of the IL-1α/VEGF signaling pathways. IL-1RA has the potential to play a role in the treatment of gastric cancer.

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Section: Discussionsupporting

confidence: 62%

Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer

Gong

et al. 2018

Int J Clin Oncol

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“…gastric, colorectal and pancreatic) [87][88][89][90]. Shintani et al [37] observed an increased CXCL1 expression in different SCC cell lines and tumor specimens and correlated it with microvessel density, leukocyte infiltration and lymph node metastasis.…”

Section: Chemokines Cxcl1 and Cxcl2mentioning

confidence: 95%

Significance of chemokine and chemokine receptors in head and neck squamous cell carcinoma: A critical review

et al. 2016

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“…CXCL1 has neutrophil chemoattractant activity, is a potent angiogenic factor, and is expressed by macrophages, neutrophils and epithelial cells [133,134]. Neutrophil granulocytes also regulate stromal interactions and were associated with worse prognoses in both breast and gastric cancers [135,136].…”

Section: In Vitro and In Vivo Evidencementioning

confidence: 99%

Somatic Mutation Theory - Why it's Wrong for Most Cancers

Brücher¹,

Jamall

2016

Cell Physiol Biochem

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Hysteron proteron reverses both temporal and logical order and this syllogism occurs in carcinogenesis and the somatic mutation theory (SMT): the first (somatic mutation) occurs only after the second (onset of cancer) and, therefore, observed somatic mutations in most cancers appear well after the early cues of carcinogenesis are in place. It is no accident that mutations are increasingly being questioned as the causal event in the origin of the vast majority of cancers as clinical data show little support for this theory when compared against the metrics of patient outcomes. Ever since the discovery of the double helical structure of DNA, virtually all chronic diseases came to be viewed as causally linked to one degree or another to mutations, even though we now know that genes are not simply blueprints, but rather an assemblage of alphabets that can, under non-genetic influences, be used to assemble a business letter or a work of Shakespearean literature. A minority of all cancers is indeed caused by mutations but the SMT has been applied to all cancers, and even to chemical carcinogenesis, in the absence of hard evidence of causality. Herein, we review the 100 year story of SMT and aspects that show why genes are not just blueprints, how radiation and mutation are associated in a more nuanced view, the proposed risk of cancer and bad luck, and the in vitro and in vivo evidence for a new cancer paradigm. This paradigm is scientifically applicable for the majority of non-heritable cancers and consists of a six-step sequence for the origin of cancer. This new cancer paradigm proclaims that somatic mutations are epiphenomena or later events occurring after carcinogenesis is already underway. This serves not just as a plausible alternative to SMT and explains the origin of the majority of cancers, but also provides opportunities for early interventions and prevention of the onset of cancer as a disease.

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CXCL1 promotes tumor growth through VEGF pathway activation and is associated with inferior survival in gastric cancer

Cited by 88 publications

References 41 publications

Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer

Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer

Significance of chemokine and chemokine receptors in head and neck squamous cell carcinoma: A critical review

Somatic Mutation Theory - Why it's Wrong for Most Cancers

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