Clinical significance of gelsolin-like actin-capping protein expression in oral carcinogenesis: an immunohistochemical study of premalignant and malignant lesions of the oral cavity.
BACKGROUND
Gelsolin-like actin-capping protein (CapG) is a ubiquitous gelsolin-family actin-modulating protein involved in cell signalling, receptor-mediated membrane ruffling, phagocytosis, and motility. CapG has generated great interest due to its oncogenic function in the control of cell migration or invasion in a variety of cancer cells. We previously applied proteomic methods to characterize differentially expressed proteins in oral squamous-cell carcinoma (OSCC) cells and detected significantly high expression levels of CapG in OSCC-derived cell lines compared to human normal oral keratinocytes. In the current study, to further determine the potential involvement of CapG in OSCC, we evaluated the status of CapG protein and mRNA expression in human oral premalignant lesions (OPLs) and primary OSCCs and correlated the results with clinicopathologic variables.


METHODS
Matched normal and tumour tissue sections of 79 human primary OSCCs and 28 OPLs were analyzed for CapG expression by immunohistochemistry (IHC). Correlations between CapG-immunohistochemical staining scores of OSCCs and clinicopathologic features were evaluated by Fisher's exact test. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to estimate CapG expression at the mRNA level.


RESULTS
In IHC, substantial up-regulation of CapG protein was observed in primary OSCCs (52%) and OPLs (64%), whereas corresponding normal tissues showed consistently weak or absent immunoreactivity of CapG. qRT-PCR data were consistent with the protein expression status. Moreover, CapG expression was correlated with the TNM stage grading of OSCCs.


CONCLUSIONS
Our finding of frequent dysregulated expression of CapG in premalignant and malignant lesions together with an association with an advanced clinical disease stage suggests that CapG could contribute to cancer development and progression and that CapG may have potential as a biomarker and a therapeutic target for OSCC.
Nomura
Hitomi
H
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. nomu@graduate.chiba-u.jp
Uzawa
Katsuhiro
K
Ishigami
Takashi
T
Kouzu
Yukinao
Y
Koike
Hirofumi
H
Ogawara
Katsunori
K
Siiba
Masashi
M
Bukawa
Hiroki
H
Yokoe
Hidetaka
H
Kubosawa
Hitoshi
H
Tanzawa
Hideki
H
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D018260:Gelsolin / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009055:Mouth / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D002352:Carrier Proteins; D018260:Gelsolin; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C066575:CAPG protein, human