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

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. 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.