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BackgroundGiven the key role of integrins in maintaining intestinal homeostasis, anti-integrin biologics in inflammatory bowel disease (IBD) are being investigated in full swing. However, the unsatisfactory efficacy and safety of current anti-integrin biologics in clinical trials limit their widespread use in clinic. Therefore, it is particularly important to find a target that is highly and specifically expressed in the intestinal epithelium of patients with IBD.MethodsThe function of integrin αvβ6 in IBD and colitis-associated carcinoma (CAC) with the underlying mechanisms has been less studied. In the present study, we detected the level of integrin β6 within inflammation including colitis tissues in human and mouse. To investigate the role of integrin β6 in IBD and CAC, integrin β6 deficient mice were hence generated based on the construction of colitis and CAC model.ResultsWe noted that integrin β6 was significantly upregulated in inflammatory epithelium of patients with IBD. Integrin β6 deletion not only reduced infiltration of pro-inflammatory cytokines, but also attenuated disruption of tight junctions between colonic epithelial cells. Meanwhile, lack of integrin β6 affected macrophage infiltration in mice with colitis. This study further revealed that lack of integrin β6 could inhibit tumorigenesis and tumor progression in CAC model by influencing macrophage polarization, which was also involved in attenuating the degree of intestinal symptoms and inflammatory responses in mice suffering from colitis.ConclusionsThe present research provides a potentially new perspective and option for the treatment of IBD and CAC.

Purpose The development of esophageal squamous cell carcinoma (ESCC) is a complicated process in which cell adhesion and motility, mediated by integrins, are involved through connecting the cytoskeleton to extracellular matrix. Different mechanisms via which integrin β6 participates in cancer invasion and metastasis have been described by numerous studies; however, the expression and clinical significance of integrin β6 in ESCC remain unknown. Methods To investigate the differential expression of integrin β6 in ESCC, qPCR and immunohistochemistry assays were performed in 10 paired human samples. A total of 137 ESCC samples were further enrolled to evaluate the expression levels of integrin β6 and its endocytic trafficking regulator HS1-associated protein X-1 (HAX-1), followed by the evaluation of their correlation with clinicopathological parameters. The overall survival was analyzed using the Kaplan–Meier method, with significant variables further evaluated by multivariate Cox regression analyses. Results The expression of integrin β6 was markedly increased in ESCC compared with matched adjacent normal tissues. Among the ESCC samples, positive expression of integrin β6 was observed in 41.6% tumors, which was associated with histological differentiation, lymph node metastasis and TNM stage. High expression of HAX-1 was detected in 47.4% tumors, and there was a positive relationship between the expression levels of integrin β6 and HAX-1. Furthermore, the expression of integrin β6 and HAX-1 were independent unfavorable indicators for prognosis. Patients with positive integrin β6 and high HAX-1 expression demonstrated worst outcomes. Conclusion The present findings suggested the predictive value of integrin β6 and HAX-1 as independent indicators of poor prognosis for patients with ESCC, both of which may contribute to the tumor proliferation and metastasis, leading to ESCC progression. Therefore, combined targeting of integrin β6 and HAX-1 may provide a potential novel approach for the treatment of ESCC.

Fanni Li,1 Yukui Shang,2 Feiyu Shi,3 Lei Zhang,3 Jun Yan,3 Qi Sun,3 Junjun She3 1Department of Talent Highland, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 2Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of ChinaCorrespondence: Qi Sun; Junjun SheDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel/Fax +86 29 85433720Email sunqi4875@163.com; junjshe@163.comPurpose: The development of esophageal squamous cell carcinoma (ESCC) is a complicated process in which cell adhesion and motility, mediated by integrins, are involved through connecting the cytoskeleton to extracellular matrix. Different mechanisms via which integrin β 6 participates in cancer invasion and metastasis have been described by numerous studies; however, the expression and clinical significance of integrin β 6 in ESCC remain unknown.Methods: To investigate the differential expression of integrin β 6 in ESCC, qPCR and immunohistochemistry assays were performed in 10 paired human samples. A total of 137 ESCC samples were further enrolled to evaluate the expression levels of integrin β 6 and its endocytic trafficking regulator HS1-associated protein X-1 (HAX-1), followed by the evaluation of their correlation with clinicopathological parameters. The overall survival was analyzed using the Kaplan–Meier method, with significant variables further evaluated by multivariate Cox regression analyses.Results: The expression of integrin β 6 was markedly increased in ESCC compared with matched adjacent normal tissues. Among the ESCC samples, positive expression of integrin β 6 was observed in 41.6% tumors, which was associated with histological differentiation, lymph node metastasis and TNM stage. High expression of HAX-1 was detected in 47.4% tumors, and there was a positive relationship between the expression levels of integrin β 6 and HAX-1. Furthermore, the expression of integrin β 6 and HAX-1 were independent unfavorable indicators for prognosis. Patients with positive integrin β 6 and high HAX-1 expression demonstrated worst outcomes.Conclusion: The present findings suggested the predictive value of integrin β 6 and HAX-1 as independent indicators of poor prognosis for patients with ESCC, both of which may contribute to the tumor proliferation and metastasis, leading to ESCC progression. Therefore, combined targeting of integrin β 6 and HAX-1 may provide a potential novel approach for the treatment of ESCC.Keywords: integrin, HAX-1, esophageal squamous cell carcinoma, prognosis

Additional file 1: Supplementary material figures S1â S10.

Interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and neovascularization have been implicated to be associated with biological processes, especially cancer progression. However, few studies have investigated the role of IL-8 in human hilar cholangiocarcinoma. In this study we detected the expression of IL-8 combined with MMP-9 and microvessel density (MVD) in hilar cholangiocarcinoma to evaluate their clinicopathological significance and prognostic value. A total of 62 patients with hilar cholangiocarcinoma who underwent curative surgery were enrolled in this study. The expression of IL-8, MMP-9 and MVD were examined immunohistochemically. The correlation of IL-8 with MMP-9 expression, MVD, clinicopathological features and survival time of patients were then analyzed. Expression of IL-8 was observed in 56.5% tumors, which was related to advanced TNM stage (P = 0.026) and tumor recurrence (P = 0.018). IL-8 had a positive correlation with MMP-9 expression and MVD. Furthermore, patients with high IL-8 expression had a significantly shorter overall survival than those with low IL-8 expression (P = 0.01). Multivariate analysis confirmed IL-8 as an independent prognostic factor (P = 0.005). In conclusion, IL-8 expression significantly correlated with MMP-9 expression and MVD, and IL-8 was a valuable prognostic factor for human hilar cholangiocarcinoma.