Tripeptidyl peptidase II (TPP2), a member of the family of eukaryotic serine peptidase, has been implicated in DNA repair, cellular division, and apoptosis. The aim of this study was to examine TPP2 expression and its functional mechanisms in oral squamous cell carcinoma (OSCC).
TPP2 mRNA and protein expression in seven OSCC-derived cells (Ca9-22, HSC-2, HSC-3, HSC-4, HO-1-N-1, H1, and Sa3) was analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Since previous studies indicated that TPP2 might control chromosomal division, we investigated cellular proliferation and spindle assembly checkpoint (SAC) molecules, MAD2 and CCNB1. In addition, we evaluated the correlation between TPP2 expression levels in primary OSCCs (n = 108 specimens) and the clinicopathologic status by immunohistochemistry (IHC).
TPP2 mRNA and protein were significantly (P < 0.05) up-regulated in OSCC-derived cells compared with human normal oral keratinocytes. Suppression of TPP2 expression with shRNA significantly (P < 0.05) inhibited cellular proliferation compared with the control cells. In addition, appropriate localization of MAD2 and up-regulation of CCNB1 were observed in TPP2 knockdown OSCC cells. IHC showed that TPP2 expression in primary OSCCs was significantly (P < 0.001) greater than that in the normal oral counterparts, and the TPP2-positive cases were significantly (P < 0.05) correlated with tumor size.
The current study showed that overexpression of TPP2 occurs frequently during oral carcinogenesis and might be associated with OSCC progression via SAC activation.
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We thank Lynda C. Charters for editing this manuscript.
Conflict of interest
We declare that we have no conflict of interest.
Katsuya Usukura and Atsushi Kasamatsu have equally contributed to this work.
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Usukura, K., Kasamatsu, A., Okamoto, A. et al. Tripeptidyl peptidase II in human oral squamous cell carcinoma. J Cancer Res Clin Oncol 139, 123–130 (2013). https://doi.org/10.1007/s00432-012-1307-y
- Spindle assembly checkpoint
- Oral squamous cell carcinoma
- shRNA experiments