Role of chemokine pathways in hepatobiliary cancer

Ehling, Josef; Tacke, Frank

doi:10.1016/j.canlet.2015.06.017

Cited by 69 publications

(68 citation statements)

References 103 publications

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“…As recently described, such mechanistic characterization could help identify targets for treatment, but to date, little work has been done on GBC [34]. Thus, the results of this study offer timely clues into the role of chemokines in the pathogenesis of GBC.…”

Section: Discussionmentioning

confidence: 73%

Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies

et al. 2016

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Most gallbladder cancer (GBC) cases arise in the context of gallstones, which cause inflammation, but few gallstone patients develop GBC. We explored inflammation/immune-related markers measured in bile and serum in GBC cases compared to gallstone patients to better understand how inflammatory patterns in these two conditions differ. We measured 65 immune-related markers in serum and bile from 41 GBC cases and 127 gallstone patients from Shanghai, China, and calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GBC versus gallstones. We then focused on the markers that were significantly elevated in bile and serum to replicate in serum from 35 GBC cases and 31 gallstone controls from Chile. Comparing the highest versus lowest quantile, 15 markers (23%) were elevated in both serum and bile from GBC versus gallstone patients in the Shanghai study (p<0.05). The strongest OR was for CXCL8 (interleukin-8) in serum (96.8, 95% CI: 11.9–790.2). Of these 15 markers, 6 were also significantly elevated in serum from Chile (CCL20, C-reactive protein, CXCL8, CXCL10, resistin, serum amyloid A). Pooled ORs from Shanghai and Chile for these 6 markers ranged from 7.2 (95% CI: 2.8–18.4) for CXCL10 to 58.2 (95% CI: 12.4–273.0) for CXCL8. GBC is associated with inflammation above and beyond that generated by gallstones alone. This local inflammatory process is reflected systemically. Future longitudinal studies are needed to identify the key players in cancer development, which may guide translational efforts to identify individuals at high risk of developing GBC.

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Section: Discussionmentioning

confidence: 73%

Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies

et al. 2016

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“…Inflammatory chemokine CXCL12 of enriched organs forms a concentration gradient and attracts CXCR4 positive tumour cells to homing by directed movement. Tumour cells moved towards the highest concentration CXCL12 gradients, realizing the directional migration and positive feedback mechanisms in an autocrine manner [46]. Hence, CXCL12/CXCR4 biological axis plays an important role in regulating specific organs metastasis.…”

Section: Discussionmentioning

confidence: 99%

DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis

Zhang

et al. 2017

Mol Cancer

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BackgroundProfiling evidences of selectin demonstrate that they play an crucial role in cancer progression and metastasis. However, DC-SIGNR as a family member of selectin participates in gastric cancer liver metastasis remains unknown.MethodsThe serum level of DC-SIGNR was evaluated in gastric cancer patients by ELISA. Manipulation DC-SIGNR expression in BGC823 and SGC7901 cell lines was mediated by lentivirus. Investigation the biological effects of DC-SIGNR were verified by MTT, wounding and transwell in vitro and experiments on animals to confirm gastric cancer liver metastasis by IVIS. Insights of the mechanism were employed microarray and bioinformatic analysis. Further to confirm the results were conducted by qRT-PCR, western blot and by flow cytometry.ResultsDC-SIGNR serum level was significantly increased in gastric cancer patients compared with healthy group. Additionally, DC-SIGNR level was associated with an advanced pathological stage in gastric cancer patients. DC-SIGNR knockdown inhibited the proliferation, migration and invasion of gastric cancer cells in vitro and suppressed the liver metastasis in vivo. While, DC-SIGNR overexpression promoted cell proliferation, migration and invasion. In mechanism, HNRNPKP2 as a lncRNA was upregulated after DC-SIGNR knockdown. Importantly, STAT5A promoted HNRNPKP2 expression after knockdown DC-SIGNR. Furthermore after HNRNPKP2 depletion, the downstream target gene CXCR4 was downregulated.ConclusionsDC-SIGNR promoted gastric cancer liver metastasis mediated with HNRNPKP2 which expression was regulated by STAT5A. And HNRNPKP2 decreased the expression of downstream target gene CXCR4. These findings indicated potential therapeutic candidates for gastric cancer liver metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0639-2) contains supplementary material, which is available to authorized users.

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“…Chemokines were frequently associated with GBC versus gallstones, suggesting that chemokine systems may be important to gallbladder carcinogenesis. Mechanistic characterization of chemokine systems may help identify targets for treatment [107]. …”

Section: Gallstone Disease Chronic Inflammation and Gallbladder Cancmentioning

confidence: 99%

The inflammatory inception of gallbladder cancer

Espinoza

Bizama

García

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

115

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Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia–dysplasia–carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted.

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Role of chemokine pathways in hepatobiliary cancer

Cited by 69 publications

References 103 publications

Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies

Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies

DC - SIGNR by influencing the lncRNA HNRNPKP2 upregulates the expression of CXCR4 in gastric cancer liver metastasis

The inflammatory inception of gallbladder cancer

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