24P - Establishment of patient-derived xenografts from malignant pleural effusion using NOG mice

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cancer biology
Thoracic malignancies
Translational Research
Presenter Tsuoyoshi Chijiwa
Citation Annals of Oncology (2016) 27 (suppl_9): ix1-ix8. 10.1093/annonc/mdw573
Authors T. Chijiwa1, M. Haraguchi2, T. Isagawa3, A. Noguchi4, M. Katayama5, N. Miyao2, M. Yoshioka2, N. Matsui6, Y. Tateishi7, H. Suemizu7, R. Yamada8, Y. Nakamura8, K. Imai8, D. Komura3, H. Katoh3, S. Ishikawa3, M. Nakamura9, Y. Miyagi8
  • 1Department Of Emergency And Critical Care Medicine, Jichi Medical University Saitama Medical Center, 3308503 - Saitama/JP
  • 2Department Of Internal Medicine, Nihon Koukan Hospital, 2100852 - Kawasaki/JP
  • 3Department Of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 1138510 - Tokyo/JP
  • 4Department Of Pathology, St. Marianna University School of Medicine, 2138511 - Kawasaki/JP
  • 5Department Of Neurosurgery, Kawasaki Municipal Hospital, 210-0013 - Kawasaki/JP
  • 6Department Of Pathology, Nihon Koukan Hospital, 2100852 - Kawasaki/JP
  • 7Laboratory Animal Research Department, Central Institute for Experimental Animals, 210-0821 - Kawasaki/JP
  • 8Research Institute, Kanagawa Cancer Center, 241-8515 - Yokohama/JP
  • 9Department Of Regenerative Medicine, Tokai University School of Medicine Isehara Campus, 259-1193 - Isehara/JP

Abstract

Background

Personalized medicine represents an ideal medical approach for cancer therapy. Xenografts derived from engrafting fresh surgical specimens directly into immunodeficient mice have recently enabled the development of more relevant in vivo models for human tumors. Patient-derived xenograft (PDX) models retain similar morphologies, heterogeneities, and molecular signatures to the original cancers, and, thus, may be used in the rapid screening of potential therapeutics. We previously reported the rapid and efficient establishment of PDXs using super-immunodeficient NOG mice (PDX/NOG). Surgical specimens are clearly necessary for establishing individual PDX/NOG using personalized medicine. In this study, we attempted to establish PDX/NOG from malignant pleural effusion (MPE) and investigated the potential of MPE-PDX/NOG for personalized anti-cancer therapies.

Methods

All MPEs were obtained from therapeutic thoracentesis with the informed consent of patients. Cell pellets combined with cancer cells and unarranged cells were generated by centrifuging MPE, and were then inoculated subcutaneously into NOG mice. The established xenograft models were confirmed pathologically after tumor tissue had been passaged three times by subcutaneous engraftment. The preservation of cancer stem cells (CSCs) was confirmed by immunohistochemical and gene expression analyses.

Results

We established 2 MPE-PDX/NOG lines (pulmonary adenocarcinoma) from 4 cases. These lines showed the histological structures of well-differentiated adenocarcinoma with murine stromal formation. The morphological characteristics of MPE-PDX/NOG were maintained for cellularity and structural heterogeneity. CSC markers (CD44, ALDH1A1, and EpCAM) were preserved in MPE-PDX/NOG tissue.

Conclusions

The establishment of PDX/NOG from MPE is efficient and as valuable as that from surgical specimens. Serial MPE-PDX/NOGs may be less invasively established from the same patient because patients with MPE may repeatedly undergo therapeutic thoracentesis. The analysis of serial MPE-PDX/NOGs will disclose characteristic changes in cancer cells affected by chemotherapies and contribute to personalized medicine.

Clinical trial indentification

Legal entity responsible for the study

Jichi Medical University

Funding

JSPS Grant-in-Aid for Scientific Research

Disclosure

All authors have declared no conflicts of interest.