High expression of CIN85 promotes proliferation and invasion of human esophageal squamous cell carcinoma.

SH3 domain­containing kinase­binding protein 1 (CIN85), an 85 kDa protein known to be a member of the signal adaptor family, is abnormally expressed in several human malignancies and has been found to be involved in the growth, migration and invasion of these tumors. The objective of the present study was to clarify the clinical significance of CIN85 in human esophageal squamous cell carcinoma (ESCC), as well as its in vitro functions. CIN85 expression was evaluated in 129 cases of ESCC and its adjacent normal tissues using immunohistochemistry to explore its clinical relevance and prognostic value. The functions of CIN85 in the ESCC TE1 cell line were analyzed in vitro using the interfering short hairpin RNA silencing technique. MTS, wound healing, clone formation and Transwell assays were used to detect the proliferation, migration and invasion of ESCC cells. CIN85 expression was identified mainly in ESCCs and their adjacent normal tissues, and the high expression of CIN85 was significantly associated with advanced Tumor Node Metastasis stage and lymph node metastasis. CIN85 gene silencing significantly inhibited TE1 cell proliferation, migration and invasion. These results demonstrated that CIN85 was highly expressed in advanced stage ESCC and lymph node metastasis, and played a critical role in tumor proliferation and progression. Therefore, CIN85 may be a promising therapeutic target for human ESCC.

Candida albicans cell wall mannoprotein synergizes with lipopolysaccharide to affect RAW264.7 proliferation, phagocytosis and apoptosis.

With the widespread use of invasive surgery, immunosuppressive therapy and broad-spectrum antibiotics, there has resulted a corresponding increase in severe systemic infections as produced by Candida albicans (C.albicans), as it combines with bacterial infections. Such infections often result in high rates of mortality. In this report, we examined the effects of the C. albicans cell wall mannoprotein (MP) on macrophage immunity. The MTS assay was used to detect cell proliferation activity and neutral red staining to observe cell phagocytosis. The Griess method was used to detect NO secretion in culture supernatants and apoptosis of macrophages were determined with use of FITC-Annexin V and PI staining. mRNA and protein expressions of JAK2, STAT3, IL-1ß, IL-6, TNF-α and iNOS in RAW264.7 cells were determined with use of RT-PCR and western blot. MP significantly promoted the proliferation of RAW264.7 cells, inhibited their phagocytic capacity, but exerted no significant effects on apoptosis of macrophages. In addition, MP not only up-regulated the expression of cytokines, but also the expressions of p-stat3 and p-jak2. Interestingly, when MP was combined with lipopolysaccharide (LPS) a markedly accentuated release of inflammatory cytokines was observed. MP promotes macrophage inflammation induced by LPS and participates in the inflammatory response. One of the potential mechanisms of this effect involves MP activation of the JAK2/STAT3 signaling pathway in RAW264.7 cells, which enables macrophages to transform from M0 to M1 and promote the occurrence of inflammation.