| Abstract |
Human papillomavirus (HPV) infection modulates several host cytokines contributing to
cancer development. Oncostatin M (OSM), an IL6 family cytokine, acts to promote cell
senescence and inhibit growth. Its dysregulation promotes cell survival, cell
proliferation and metastasis in various malignancies. The effect of HPV on OSM
dysregulation has not been investigated. To elucidate this, immunohistochemistry was
used on formalinfixed, paraffinembedded oral squamous cell carcinoma (OSCC)
tissues: HPVpositive (50) and HPVnegative (50) cases. Immortalized human cervical
keratinocytes expressing HPV16E6 (HCK1T, TetOn system) were used to demonstrate
the role of HPV16E6 in OSM expression. In addition, a vector containing HPV16E6/E7
was transiently transfected into oral cancer cell lines. Cell viability, cellcycle
progression and cell migration were evaluated using flow cytometry and a wound
healing assay, respectively. The results showed various intensities of OSM expression in
OSCC. Interestingly, the median percentages of strongly stained cells were significantly
higher in HPVpositive OSCCs than in HPVnegative OSCCs. To explore the role of
HPV oncoproteins on OSM expression, the expression of HPV16E6 in the HCK1T TetOn condition was induced by doxycycline and HPV16E6 was found to significantly
upregulate levels of OSM mRNA and protein, with concomitant upregulation of cMyc.
In addition, the levels of OSM mRNA and protein in E6/E7 transiently transfected oral
cancer cells also gradually increased in a timedependent manner and these transfected
cells showed greater viability and higher migration rates and cellcycle progression than
controls. This result demonstrates that HPV16 oncoproteins upregulate OSM and play
an important role to promote OSCC development. |
Publication
Journal Publication
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