Journal article
Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis
Oncotarget, Vol.7(17), pp.24194-24207
04/26/2016
DOI: 10.18632/oncotarget.8254
PMCID: PMC5029694
PMID: 27013584
Abstract
Human papillomavirus induced (HPV+) cancer incidence is rapidly rising, comprising 60-80% of oropharyngeal squamous cell carcinomas (OPSCCs); while rare, recurrent/metastatic disease accounts for nearly all related deaths. An in vivo pre-clinical model for these invasive cancers is necessary for testing new therapies. We characterize an immune competent recurrent/metastatic HPV+ murine model of OPSSC which consists of four lung metastatic (MLM) cell lines isolated from an animal with HPV+ OPSCC that failed cisplatin/radiation treatment. These individual metastatic clonal cell lines were tested to verify their origin (parental transgene expression and define their physiological properties: proliferation, metastatic potential, heterogeneity and sensitivity/resistance to cisplatin and radiation. All MLMs retain expression of parental HPV16 E6 and E7 and degrade P53 yet are heterogeneous from one another and from the parental cell line as defined by Illumina expression microarray. Consistent with this, reverse phase protein array defines differences in protein expression/activation between MLMs as well as the parental line. While in vitro growth rates of MLMs are slower than the parental line, in vivo growth of MLM clones is greatly enhanced. Moreover, in vivo resistance to standard therapies is dramatically increased in 3 of the 4 MLMs. Lymphatic and/or lung metastasis occurs 100% of the time in one MLM line. This recurrent/metastatic model of HPV+ OPSCC retains the characteristics evident in refractory human disease (heterogeneity, resistance to therapy, metastasis in lymph nodes/lungs) thus serving as an ideal translational system to test novel therapeutics. Moreover, this system may provide insights into the molecular mechanisms of metastasis.
Details
- Title: Subtitle
- Metastatic model of HPV+ oropharyngeal squamous cell carcinoma demonstrates heterogeneity in tumor metastasis
- Creators
- Daniel W Vermeer - Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USAJoseph D Coppock - Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USAErliang Zeng - Department of Computer Science, University of South Dakota, Vermillion, South Dakota, USAKimberly M Lee - Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USAWilliam C Spanos - Department of Otolaryngology/Head and Neck Surgery, Sanford Health, Sioux Falls, South Dakota, USAMichael D Onken - Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USARavindra Uppaluri - Otolaryngology, Washington University School of Medicine, St. Louis, Missouri, USAJohn H Lee - Department of Otolaryngology/Head and Neck Surgery, Sanford Health, Sioux Falls, South Dakota, USAPaola D Vermeer - Cancer Biology Research Center, Sanford Research, Sioux Falls, South Dakota, USA
- Resource Type
- Journal article
- Publication Details
- Oncotarget, Vol.7(17), pp.24194-24207
- DOI
- 10.18632/oncotarget.8254
- PMID
- 27013584
- PMCID
- PMC5029694
- NLM abbreviation
- Oncotarget
- ISSN
- 1949-2553
- eISSN
- 1949-2553
- Publisher
- United States
- Grant note
- P30 CA016672 / NCI NIH HHS P20 GM103548 / NIGMS NIH HHS P20 GM103620 / NIGMS NIH HHS R01 DE018386 / NIDCR NIH HHS R01 CA193522 / NCI NIH HHS K08 CA149078 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 04/26/2016
- Academic Unit
- Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Biostatistics; Dental Research
- Record Identifier
- 9984065468602771
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