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Published on: July 25, 2011
Tripeptidyl peptidase II in human oral squamous cell carcinoma
Katsuya Usukura1, Atsushi Kasamatsu, Atsushi Okamoto
1Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Purpose:
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).
Methods:
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).
Results:
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.
Conclusion:
The current study showed that overexpression of TPP2 occurs frequently during oral carcinogenesis and might be associated with OSCC progression via SAC activation.
Insights
Overexpression of tripeptidyl peptidase II (TPP2) is frequent in oral squamous cell carcinoma (OSCC) and linked to tumor progression. TPP2 may drive OSCC development through spindle assembly checkpoint activation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Tripeptidyl peptidase II (TPP2) is a serine peptidase involved in DNA repair, cell division, and apoptosis.
- Understanding TPP2's role in oral squamous cell carcinoma (OSCC) is crucial for targeted therapies.
Purpose of the Study:
- To investigate TPP2 expression levels in OSCC.
- To elucidate the functional mechanisms of TPP2 in OSCC progression.
Main Methods:
- Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting were used to analyze TPP2 expression in OSCC cell lines.
- Cellular proliferation and spindle assembly checkpoint (SAC) molecules (MAD2, CCNB1) were assessed following TPP2 knockdown.
- Immunohistochemistry (IHC) evaluated TPP2 expression in 108 primary OSCC specimens and correlated it with clinicopathologic features.
Main Results:
- TPP2 mRNA and protein were significantly upregulated in OSCC cells compared to normal oral keratinocytes.
- TPP2 suppression inhibited cellular proliferation and affected MAD2 localization and CCNB1 expression in OSCC cells.
- Elevated TPP2 expression in primary OSCCs correlated significantly with larger tumor size.
Conclusions:
- Overexpression of TPP2 is a common event in oral carcinogenesis.
- TPP2 may contribute to OSCC progression by activating the spindle assembly checkpoint (SAC).
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