Establishment and validation of patient-derived xenograft model of oral mucosal melanoma

doi:10.19438/j.cjoms.2017.06.001

Abstract

Abstract: PURPOSE: To establish and validate patient-derived xenograft (PDX) model of oral mucosal melanoma (OMM). METHODS: Four primary OMM specimens were implanted into immune-deficient nude mice subcutaneously, the mice were evaluated for tumor growth, stable xenograft tumor models and were passaged. Histopathological characteristics were observed by H-E staining. OMM-associated clinical markers (HMB-45, Melan-A, S-100 and Ki-67) were detected by immunohistochemistrical staining. RESULTS: OMM samples from 4 patients were implanted subcutaneously and passaged for expansion successfully. Histopathologically and immunohistochemistrically, PDX models showed similar morphology and HMB-45, Melan-A, S-100 and Ki-67 protein expression to the primary tumor. CONCLUSIONS: Four xenograft models were successfully established, in which the histopathological and molecular features of the primary tumors are preserved through passaging, which provid promising preclinical models for translational research of OMM.

Key words: Oral mucosal melanoma, Patient-derived xenograft model, Nude mice

CLC Number:

R739.8

TAO Wen-jie, HAN Yong, ZHOU Rong, SHI Chao-ji, HONG Duo, LI Jiang, SUN Shu-yang, ZHANG Zhi-yuan. Establishment and validation of patient-derived xenograft model of oral mucosal melanoma[J]. China Journal of Oral and Maxillofacial Surgery, 2017, 15(6): 481-487.

References

[1] Yang X, Ren GX, Zhang CP, et al. Neck dissection and post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin protocol are useful for oral mucosal melanoma[J]. BMC Cancer, 2010, 10: 623.
[2] 李丽, 孔燕, 李海夫, 等. 262例中国人黑色素瘤C-KIT基因扩增分析 [J]. 临床肿瘤学杂志, 2010, 15(5): 385-389.
[3] 吴云腾, 任国欣, 孙沫逸, 等. 中国头颈黏膜黑色素瘤临床诊治专家共识 [J]. 中国口腔颌面外科杂志, 2015, 13(3): 262-269.
[4] Sun CZ, Chen YF, Jiang YE, et al. Treatment and prognosis of oral mucosal melanoma [J]. Oral Oncol, 2012, 48(7): 647-652.
[5] 郭伟, 任国欣, 王新, 等. 口腔颌面-头颈恶性黑色素瘤综合治疗探索及进展[C]. 上海：国际暨全国第十一届头颈肿瘤学术大会论文集, 2011: 36-39.
[6] Tentler JJ, Tan AC, Weekes CD, et al. Patient-derived tumour xenografts as models for oncology drug development [J]. Nat Rev Clin Oncol, 2012, 9(6): 338-350.
[7] Hidalgo M, Amant F, Biankin AV, et al. Patient-derived xenograft models: an emerging platform for translational cancer research [J]. Cancer Discov, 2014, 4(9): 998-1013.
[8] Aparicio S, Hidalgo M, Kung AL. Examining the utility of patient-derived xenograft mouse models [J]. Nat Rev Cancer, 2015, 15(5): 311-316.
[9] Stewart EL, Mascaux C, Pham NA, et al. Clinical utility of patient-derived xenografts to determine biomarkers of prognosis and map resistance pathways in EGFR-mutant lung adenocarcinoma [J]. J Clin Oncol, 2015, 33(22): 2472-2480.
[10] Gao H, Korn JM, Ferretti S, et al. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response [J]. Nat Med, 2015, 21(11): 1318-1325.
[11] Bertotti A, Migliardi G, Galimi F, et al. A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer [J]. Cancer Discov, 2011, 1(6): 508-523.
[12] Marangoni E, Poupon MF. Patient-derived tumour xenografts as models for breast cancer drug development [J]. Curr Opin Oncol, 2014, 26(6): 556-561.
[13] Laurent C, Gentien D, Piperno-Neumann S, et al. Patient-derived xenografts recapitulate molecular features of human uveal melanomas [J]. Mol Oncol, 2013, 7(3): 625-636.
[14] Sun S, Zhang Z. Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research and a new co-clinical model for treatment optimization [J]. Front Med, 2016, 10(1): 104-110.
[15] Bastian BC. The molecular pathology of melanoma: an integrated taxonomy of melanocytic neoplasia [J]. Annu Rev Pathol, 2014, 9: 239-271.
[16] Shultz LD, Goodwin N, Ishikawa F, et al. Human cancer growth and therapy in immunodeficient mouse models [J]. Cold Spring Harb Protoc, 2014, 2014(7): 694-708.
[17] 李克娟, 黄昊, 高苒. 人源肿瘤异种移植模型在精准肿瘤医学中的研究进展[J]. 中国比较医学杂志, 2017, 27(1): 91-98.
[18] Jin K, Teng L, Shen Y, et al. Patient-derived human tumour tissue xenografts in immunodeficient mice: a systematic review [J]. Clin Transl Oncol, 2010, 12(7): 473-480.
[19] 刘情, 郑琳, 张灏. 人源性肿瘤组织异种移植模型的研究进展 [J]. 转化医学杂志, 2014, 3(2): 65-68.
[20] Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models [J]. Cancer Res, 2013, 73(17): 5315-5319.
[21] Dong X, Guan J, English JC, et al. Patient-derived first generation xenografts of non-small cell lung cancers: promising tools for predicting drug responses for personalized chemotherapy [J]. Clin Cancer Res, 2010, 16(5): 1442-1451.
[22] Julien S, Merino-Trigo A, Lacroix L, et al. Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer [J]. Clin Cancer Res, 2012, 18(19): 5314-5328.
[23] Zhang X, Claerhout S, Prat A, et al. A renewable tissue resource off phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models [J]. Cancer Res, 2013, 73(15): 4885-4897.
[24] Landis MD, Lehmann BD, Pietenpol JA, et al. Patient-derived breast tumor xenografts facilitating personalized cancer therapy [J]. Breast Cancer Res, 2013, 15(1): 201.
[25] Ricci F, Bizzaro F, Cesca M, et al. Patient-derived ovarian tumor xenografts recapitulate human clinicopathology and genetic alterations [J]. Cancer Res, 2014, 74(23): 6980-6990.
[26] Girotti MR, Gremel G, Lee R, et al. Application of sequencing, liquid biopsies, and patient-derived xenografts for personalized medicine in melanoma [J]. Cancer Discov, 2016, 6(3):286-299.
[27] Townsend EC, Murakami MA, Christodoulou A, et al. The public repository of xenografts enables discovery and randomized Phase II-like trials in mice [J]. Cancer Cell, 2016, 29(4): 574-586.
[28] Bruna A, Rueda OM, Greenwood W, et al. A biobank of breast cancer explants with preserved intra-tumor heterogeneity to screen anticancer compounds [J]. Cell, 2016, 167(1): 260-274.
[29] Nardella C, Lunardi A, Patnaik A, et al. The APL paradigm and the "co-clinical trial" project[J]. Cancer Discov, 2011, 1(2): 108-116.