CALRETICULIN EXPRESSION IS REQUIRED FOR ORAL CANCER CELL PROLIFERATION AND MIGRATION AND CORRELATED WITH CLINICOPATHOLOGIC FEATURES IN ORAL SQUAMOUS CELL CARCINOMA PATIENTS

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Abstract

Background

Oral squamous cell carcinoma (OSCC) has emerged as one of the major malignant tumors of the head and neck cancers. However, little is known about the molecular mechanism behind tumorigenesis of OSCC. The aim of this study was to identify cancer-associated proteins by comparing the proteomes of OSCC and adjacent non-cancerous-matched tissues (NCMTs).

Methods

We used two-dimensional electrophoresis coupled with mass spectrometry to identify differentially expressed proteins. Later we carried out MTT assay and transwell-based migration assay to study proliferation and migration of calreticulin knockdown OSCC cells, respectively. Finally, we conducted immunohistochemistry (IHC) to reveal calreticulin expression in OSCC and NCMT sections and analyze the correlations with multiple clinicopathological parameters.

Results

After identification of the candidate proteins by LC/MS/MS, calreticulin was found to be upregulated in OSCC specimens. Calreticulin was differentially expressed in fresh tumor samples and six OSCC cell lines but not in adjacent NCMTs. Functional characterization of calreticulin by siRNA knockdown revealed its requirement for oral cancer cell proliferation and migration. Furthermore, using oral tissue microarray and IHC, we demonstrated that the positive staining of calreticulin in tumor specimens (99 of 103) was significantly higher than that in NCMTs (29 of 92) (P < 0.001). More importantly, we found that the intensity of calreticulin expression was positively correlated with various clinicopathological parameters including larger tumor size (T) (P = 0.0241), lower degree of tumor differentiation (P = 0.0007) and extracapsular spread (ECS) (P = 0.01).

Conclusions

Together, our data suggest that calreticulin could play a key role in oral cancer development and could be a prognostic biomarker for OSCC patients.

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