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Effect of human papillomavirus 16 oncoproteins on oncostatin M upregulation in oral squamous cell carcinoma

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Abstract

Human papillomavirus (HPV) infection modulates several host cytokines contributing to cancer development. Oncostatin M (OSM), an IL-6 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 formalin-fixed, paraffin-embedded oral squamous cell carcinoma (OSCC) tissues: HPV-positive (50) and HPV-negative (50) cases. Immortalized human cervical keratinocytes expressing HPV16E6 (HCK1T, Tet-On 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, cell-cycle 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 HPV-positive OSCCs than in HPV-negative OSCCs. To explore the role of HPV oncoproteins on OSM expression, the expression of HPV16E6 in the HCK1T Tet-On condition was induced by doxycycline and HPV16E6 was found to significantly upregulate levels of OSM mRNA and protein, with concomitant upregulation of c-Myc. In addition, the levels of OSM mRNA and protein in E6/E7 transiently transfected oral cancer cells also gradually increased in a time-dependent manner and these transfected cells showed greater viability and higher migration rates and cell-cycle progression than controls. This result demonstrates that HPV16 oncoproteins upregulate OSM and play an important role to promote OSCC development.

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Abbreviations

Dox:

Doxycycline

FFPE:

Formalin-fixed, paraffin-embedded

HCK1T:

Immortalized human cervical keratinocyte

HPV:

Human papillomavirus

IHC:

Immunohistochemistry

ISH:

In situ hybridization

OSCC:

Oral squamous cell carcinoma

OSM:

Oncostatin M

TCA:

Trichloroacetic acid

TMA:

Tissue microarray

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Acknowledgments

This project was supported by Grant of Faculty of Medicine, Khon Kaen University (Grant Number IN59117), and Khon Kaen University, Thailand (Grant Number 581202). We would like to acknowledge Prof. David Blair, for editing the MS via Publication Clinic KKU, Thailand.

Author information

Authors and Affiliations

  1. Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

    Jureeporn Chuerduangphui, Chamsai Pientong, Piyawut Swangphon, Weerayut Wongjampa & Tipaya Ekalaksananan

  2. Department of Oral Diagnosis, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand

    Ponlatham Chaiyarit

  3. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

    Natcha Patarapadungkit

  4. Anatomical Pathology Unit, Khon Kaen Hospital, Khon Kaen, Thailand

    Apinya Chotiyano

  5. Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

    Bunkerd Kongyingyoes

  6. Department of Epidemiology, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand

    Supannee Promthet

  7. HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand

    Jureeporn Chuerduangphui, Chamsai Pientong, Natcha Patarapadungkit, Apinya Chotiyano, Supannee Promthet, Piyawut Swangphon, Weerayut Wongjampa & Tipaya Ekalaksananan

  8. Research Group of Chronic Inflammatory Oral Diseases and Systemic Diseases Associated with Oral Health, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand

    Ponlatham Chaiyarit

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  1. Jureeporn Chuerduangphui
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  2. Chamsai Pientong
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Corresponding author

Correspondence to Tipaya Ekalaksananan.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval was given by the Khon Kaen University Ethics Committee (No. HE 581211). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study, giving their authorization to access their clinical information and tumor samples for research purpose.

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Chuerduangphui, J., Pientong, C., Chaiyarit, P. et al. Effect of human papillomavirus 16 oncoproteins on oncostatin M upregulation in oral squamous cell carcinoma. Med Oncol 33, 83 (2016). https://doi.org/10.1007/s12032-016-0800-6

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  • DOI: https://doi.org/10.1007/s12032-016-0800-6

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