IL-6 Expression Regulates Tumorigenicity and Correlates with Prognosis in Bladder Cancer

Abstract

Identification of potential tumor markers will help stratify and identify a tumor's malignant potential and its response to specific therapies. IL-6 has been reported to be a predictor in various cancers. Therefore, the present study was performed to highlight the role of IL-6 in improving treatment and determining prognosis of bladder cancer. The human bladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments, in which biological changes after experimental manipulation of IL-6 were explored, including tumor behavior and related signaling in bladder cancer. In addition, clinical specimens from 85 patients with muscle-invasive, and 50 with non-muscle invasive bladder cancers were selected for immunohistochemical staining to evaluate the predictive capacity of IL-6 in relation to clinical outcome. The data revealed that IL-6 was overexpressed in the bladder cancer specimens compared with non-malignant tissues at both mRNA and protein levels. Positive staining of IL-6 was significantly correlated with higher clinical stage, higher recurrence rate after curative treatment, and reduced survival rate. Tumor growth and invasive capability were attenuated when IL-6 was blocked. The underlying changes included decreased cell proliferation, less epithelial-mesenchymal transition (EMT), decreased DNA methyltransferase 1 expression and attenuated angiogenesis. In conclusion, our findings showed that IL-6 could be a significant predictor for clinical stage and prognosis of bladder cancer. Moreover, targeting IL-6 may be a promising strategy for treating bladder cancer.

Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression

“…These molecules modulate growth, proliferative, migration, and apoptotic pathways, often resulting in metastasis and advanced stage disease (33)(34)(35)(36)(37)(38)(39)(40). Next, we evaluated expression of a panel of cytokines associated with disease progression using pancreas tumor tissues from the same cohort in the previous section by qPCR.…”

A Novel IL6 Antibody Sensitizes Multiple Tumor Types to Chemotherapy Including Trastuzumab-Resistant Tumors

“…Elevated levels of IL6 are associated with poor prognosis in cancers of the lung, colon, kidney, bladder, and others (28)(29)(30). Thus, therapeutics targeting IL6 and IL6 signaling components are also being tested in clinical trials for cancer.…”

Interleukin-12 and Interleukin-6 Gene Polymorphisms and Risk of Bladder Cancer in the Iranian Population

“…Today, the important role of pro-inflammatory cytokines during tumor development is increasingly gaining interest. IL-6 is a pleiotropic inflammatory cytokine, which is regarded as an important tumor-promoting factor in the development and progression of various types of human cancer, including bladder cancer (Waldner et al, 2012;Zhu et al, 2012;Chen et al, 2013). Moreover, increased IL-6 serum levels were reported to be associated with metastasis and poor prognosis of prostate, ovarian, and bladder cancers (George et al, 2005).…”