Establishment of Novel Neuroendocrine Carcinoma Patient-Derived Xenograft Models for Receptor Peptide-Targeted Therapy

Catherine G. Tran, Luis C. Borbon, Jacqueline L. Mudd, Ellen Abusada, Solmaz Aghaamiri, Sukhen C. Ghosh, Servando Hernandez Vargas, Guiying Li, Gabriella V. Beyer, Mary McDonough, Rachel Li, Carlos H.F. Chan, Susan A. Walsh, Thaddeus J. Wadas, Thomas O’dorisio, M. Sue O’dorisio, Ramaswamy Govindan, Paul F. Cliften, Ali Azhdarinia, Andrew M. BellizziRyan C. Fields, James R. Howe, Po Hien Ear

Research output: Contribution to journalArticlepeer-review

Abstract

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consist-ing of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for studying GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To ad-dress this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of six mice developed tumors (NEC913 and NEC1452). Over 80% of NEC913 and NEC1452 tumor cells stained positive for Ki67. NEC913 PDX tumors expressed neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and somatostatin receptor-2 (SSTR2), whereas NEC1452 PDX tumors did not express SSTR2. Exome sequencing revealed loss of TP53 and RB1 in both NEC tumors. To demonstrate an application of these novel NEC PDX models for SSTR2-targeted peptide imaging, the NEC913 and NEC1452 cells were bilaterally injected into mice. Near infrared-labelled octreotide was administered and the fluorescent signal was specifically observed for the NEC913 SSTR2 positive tumors. These 2 GEP NEC PDX models serve as a valuable resource for GEP NEN therapy testing.

Original languageEnglish
Article number1910
JournalCancers
Volume14
Issue number8
DOIs
StatePublished - Apr 1 2022

Keywords

  • gastroenteropancreatic neuroendocrine neoplasms
  • near infrared-labelled octreotide analog
  • patient-derived xenograft
  • somatostatin receptor-2
  • tumor spheroids

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