Comprehensive characterization of chemotherapeutic efficacy on metastases in the established gastric neuroendocrine cancer patient derived xenograft model

// Jiahua Jiang 1,* , Daisy Dandan Wang 2,* , Mengmeng Yang 1,* , Dawei Chen 1 , Liang Pang 1 , Sheng Guo 1 , Jie Cai 1 , Jean-Pierre Wery 1 , Linda Li 2 , Henry Qixiang Li 1,3 and Peter Ping Lin 2 1 Crown Bioscience, Santa Clara, California, USA 2 Cytelligen, San Diego, California, USA 3 State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China * These authors contributed equally to this study Correspondence to: Peter Ping Lin, email: // Henry Qixiang Li, email: // Keywords : CTC subtypes, metastatic PDX, iFISH, chemoresistance, in situ phenotyping and karyotyping Received : February 07, 2015 Accepted : March 10, 2015 Published : March 30, 2015 Abstract The HuPrime ® human gastric neuroendocrine carcinoma derived xenograft model GA0087 was established in this study. GA0087 PDX model showed high gene expression of vascular endothelial growth factors (VEGF)-A and B, and high potential of lung metastasis. Circulating tumor cells (CTCs) with either large or small size, circulating tumor microemboli (CTM) and lung metastatic lesions were detected in GA0087 PDX mice. The number of CTC correlated to the number of metastatic nodules in lung. Both primary tumor growth and metastasis in terms of the number of dynamically monitored CTCs and metastatic nodules were effectively suppressed by Cisplatin. Diverse subtypes of CTCs in the context of sensitivity to Cisplatin were specifically identified by subtraction enrichment (SE) integrated with in situ Phenotyping of cytokeratin 18 (CK18) and Karyotyping of chromosome 8 ( in situ PK CTC by CK-iFISH). All the CK18-/diploid and majority of CK18+/diploid CTC subtypes were chemosensitive, whereas a higher percentage of CK18+/multiploid subtype of CTC were Cisplatin-insensitive. Combined histopathological examination of metastatic lesion and in situ PK CTC in a metastatic PDX (mPDX) tumor model are of particular significance, and may provide an unique and robust platform for cancer research as well as pre-clinical evaluation of therapeutic efficacy of new anti-cancer drugs.