Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts.
Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts.
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DOI：
10.1158/1078-0432.ccr-12-2746
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发表时间：
2013-02-15
期刊：
影响因子：
--
通讯作者：
Lambert PF
中科院分区：
文献类型：
--
作者：
Kimple RJ;Harari PM;Torres AD;Yang RZ;Soriano BJ;Yu M;Armstrong EA;Blitzer GC;Smith MA;Lorenz LD;Lee D;Yang DT;McCulloch TM;Hartig GK;Lambert PF
To develop a clinically relevant model system to study head and neck squamous cell carcinoma (HNSCC), we have established and characterized a direct-from-patient, tumorgraft model of Human Papillomavirus (HPV)-positive and HPV-negative cancers. Patients with newly diagnosed or recurrent HNSCC were consented for donation of tumor specimens. Surgically obtained tissue was implanted subcutaneously into immunodeficient mice. During subsequent passages, both formalin-fixed/paraffin embedded as well as flash frozen tissues were harvested. Tumors were analyzed for a variety of relevant tumor markers. Tumor growth rates and response to radiation, cisplatin, or cetuximab were assessed and early passage cell strains were developed for rapid testing of drug sensitivity. Tumorgrafts have been established in 22 of 26 patients to date. Significant diversity in tumorgraft tumor differentiation was observed with good agreement in degree of differentiation between patient tumor and tumorgraft (Kappa 0.72). Six tumorgrafts were HPV-positive on the basis of p16 staining. A strong inverse correlation between tumorgraft p16 and p53 or Rb was identified (Spearman correlations p=0.085 and p=0.002, respectively). Significant growth inhibition of representative tumorgrafts was demonstrated with cisplatin, cetuximab or radiation treatment delivered over a two-week period. Early passage cell strains showed high consistency in response to cancer therapy between tumorgraft and cell strain. We have established a robust human tumorgraft model system for investigating HPV-positive and HPV-negative HNSCC. These tumorgrafts show strong correlation with the original tumor specimens and provide a powerful resource for investigating mechanisms of therapeutic response as well as preclinical testing.
