An in vitro multistep carcinogenesis model for both HPV-positive and -negative human oral squamous cell carcinoma

Aims and objective: Human papilloma virus (HPV) has also been postulated to have a role in oral carcinogenesis. Our goal is to develop an appropriate model for recapitulating development and progression of both HPV-positive and -negative human OSCCs.

Materials and methods: To elucidate the carcinogenesis process, we newly established human tongue keratinocytes (HTK) cell lines derived from tongue mucosa with retroviral vectors expressing either HPV16 E6/E7 or a mutant CDK4 (CDK4R24C), cyclin D1 and human telomerase reverse transcriptase (hTERT).

Results: HTK-16E6E7 and HTK-CDK4R24C/cyclinD1/hTERT (termed HTK-K4DT) retaining most of the original characteristics of primary tongue keratinocytes showed no tumorigenicity in xeno-transplanted mice. Additional transduction of oncogenic Hras or erbB1 together with c-myc into the HTK-16E6E7 and HTK-K4DT expressing DNp53 (dominant negative form of p53) showed the anchorage-independent growth and subcutaneous tumor formation in nude mice. Orthotopic transplantation of HTK-K4DT-DNp53-Hras V12 -c-myc-wt (wild type c-myc) and HTK-K4DT-DNp53-erbB1-c-myc T58A (mutant-c-myc) cells resulted in local growth of tumors in all the mice tested and some of them yielded regional metastases in 2–3 weeks.

Conclusion: Our experimental model should facilitate further studies to understand genesis of OSCCs and hopefully will assist in the evaluation of new therapies.

Conflict of interest: None declared.

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Jan 27, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on An in vitro multistep carcinogenesis model for both HPV-positive and -negative human oral squamous cell carcinoma
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