Junko Mukohyama1, Yohei Shimono2, Kimihiro Yamashita3, Yasuo Sumi3, Toru Mukohara4, Hironobu Minami4, Yoshihiro Kakeji3. 1. Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 2. Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan yshimono@med.kobe-u.ac.jp. 3. Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 4. Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan Cancer Center, Kobe University Hospital, Kobe, Japan.
Abstract
BACKGROUND: Cancer stem cells (CSCs) have a high tumorigenic ability to form patient-derived tumor xenografts (PDXs). PDXs are an attractive pre-clinical model, but gene expression and biological behavior of cancer cells in the tumor will change during establishment and passage of PDXs. MATERIALS AND METHODS: Human colon cancer PDX was established and passaged either subcutaneously or orthotopically into the murine intestine. Histology and flow cytometric profile of the surgical specimen and the PDX were analyzed. CSCs were then isolated from the tumors and their microRNA (miRNA) expression was analyzed by semi-quantitative polymerase chain reaction. RESULTS: The surgical specimens and PDXs were histologically similar. The size of CSC population increased and expression of miRNAs in CSCs changed in the passaged PDXs. Expression of oncogenic miRNAs was highly up-regulated in the CSCs of the orthotopically passaged PDXs. CONCLUSION: The xenotransplantation site and the number of tumor passages affect the miRNA expression of human colon CSCs. Copyright
BACKGROUND:Cancer stem cells (CSCs) have a high tumorigenic ability to form patient-derived tumor xenografts (PDXs). PDXs are an attractive pre-clinical model, but gene expression and biological behavior of cancer cells in the tumor will change during establishment and passage of PDXs. MATERIALS AND METHODS:Humancolon cancer PDX was established and passaged either subcutaneously or orthotopically into the murine intestine. Histology and flow cytometric profile of the surgical specimen and the PDX were analyzed. CSCs were then isolated from the tumors and their microRNA (miRNA) expression was analyzed by semi-quantitative polymerase chain reaction. RESULTS: The surgical specimens and PDXs were histologically similar. The size of CSC population increased and expression of miRNAs in CSCs changed in the passaged PDXs. Expression of oncogenic miRNAs was highly up-regulated in the CSCs of the orthotopically passaged PDXs. CONCLUSION: The xenotransplantation site and the number of tumor passages affect the miRNA expression of humancolon CSCs. Copyright