Evaluation of the prognostic and therapeutic potential of inhibin beta B for oral squamous cell carcinoma.

Background/purpose: Oral squamous cell carcinoma (OSCC) is a common cancer worldwide, and its metastasis is difficult to predict and prevent. Inhibin beta B (INHBB) protein has been linked to cancer prognosis and epithelial-mesenchymal transition (EMT). However, previous study about INHBB expression focused on patients in a single region while the risk factors vary among regions. This study aimed to provide a broader perspective on INHBB expression in OSCC. Materials and methods: Tissue micro-arrays comprising 118 specimens were subjected to immunohistochemistry, and all slides were quantified using StrataQuest software. Results: The ratio of INHBB-positive cells to total cells was significantly higher in OSCC samples than in normal samples, and the intensity of INHBB expression was significantly greater in the late-stage OSCC. After classifying specimens into high and low INHBB expression groups, a significant association with clinical staging was found. Though a previous study suggested that menin regulates INHBB, menin expression was not detected in specimens. Conclusion: The ratio of INHBB-positive cells in OSCC may be druggable for targeting tumor cells or assisting in diagnosis, and the intensity of INHBB expression may provide prognostic information for predicting potential metastasis. Moreover, the regulatory mechanism of INHBB in OSCC remains unclear and requires further investigation.

Fibroblast growth factor 5 expression predicts the progression of oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Fibroblast growth factor (FGF) 5 is a member of the FGF family that functions as a regulator of tissue growth and regeneration. Aberrant FGF5 expression has been previously associated with the progression of a number of different malignancies. However, its potential role in oral cancer remains unclear. In this study, we explored the relationship between the expression of FGF5 protein in oral squamous cell carcinomas (OSCCs) and the clinicopathological parameters of OSCCs and whether the expression of FGF5 protein in OSCCs could be a prognostic factor for OSCC patients. METHODS: The FGF5 protein expression was examined in 64 OSCC and 34 normal oral mucosal specimens by immunohistochemical staining. Stress induced upregulation and intracellular redistribution of FGF5 were verified using xenograft animal model and OSCC cell lines. RESULTS: The mean FGF5 protein labelling index was significantly higher in OSCC than in normal oral mucosal samples, with high FGF5 protein labelling index (>58%) being correlated with advanced stage and poor survival of OSCC patients. Apart from the peri-cytoplasmic staining pattern characteristic of paracrine growth factors, FGF5 protein was localized as distinct punctate structures in the cytoplasm of advanced stage or stressed-induced cells. This redistribution and upregulation of FGF5 protein could be sustained after termination of the stress induction in cell line and xenograft animal models. CONCLUSION: FGF5 can be induced by cellular stress and risk factors of OSCC, where high expression levels of FGF5 is potentially a useful parameter for predicting OSCC progression and patient survival.

Acidosis promotes the metastatic colonization of lung cancer via remodeling of the extracellular matrix and vasculogenic mimicry.

Acidosis is a hallmark of the tumor microenvironment caused by the metabolic switch from glucose oxidative phosphorylation to glycolysis. It has been associated with tumor growth and progression; however, the precise mechanism governing how acidosis promotes metastatic dissemination has yet to be elucidated. In the present study, a long­term acidosis model was established using patient­derived lung cancer cells, to identify critical components of metastatic colonization via transcriptome profiling combined with both in vitro and in vivo functional assays, and association analysis using clinical samples. Xenograft inoculates of 1 or 10 acidotic cells mimicking circulating tumor cell clusters were shown to exhibit increased tumor incidence compared with their physiological pH counterparts. Transcriptomics revealed that profound remodeling of the extracellular matrix (ECM) occurred in the acidotic cells, including upregulation of the integrin subunit α­4 (ITGA4) gene. In clinical lung cancer, ITGA4 expression was found to be upregulated in primary tumors with metastatic capability, and this trait was retained in the corresponding secondary tumors. Expression of ITGA4 was markedly upregulated around the vasculogenic mimicry structures of the acidotic tumors, while acidotic cells exhibited a higher ability of vasculogenic mimicry in vitro. Acidosis was also found to induce the enrichment of side population cells, suggesting an enhanced resistance to noxious attacks of the tumor microenvironment. Taken together, these results demonstrated that acidosis actively contributed to tumor metastatic colonization, and novel mechanistic insights into the therapeutic management and prognosis of lung cancer were discussed.