Celia Chao1, Steve G Widen2, Thomas G Wood2, John R Zatarain3, Paul Johnson3, Aakash Gajjar3, Guillermo Gomez3, Suimin Qiu4, Jill Thompson2, Heidi Spratt5, Mark R Hellmich3. 1. Department of Surgery, University of Texas Medical Branch, Galveston, TX, U.S.A. cechao@utmb.edu. 2. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, U.S.A. 3. Department of Surgery, University of Texas Medical Branch, Galveston, TX, U.S.A. 4. Department of Surgical Pathology, University of Texas Medical Branch, Galveston, TX, U.S.A. 5. Department of Preventative Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, U.S.A.
Abstract
BACKGROUND/AIM: Patient-derived xenografting (PDX) of human colorectal cancer (CRC) is the preferred experimental model to study tumor response to therapeutic agents. Gradually, human stromal cells are replaced by mouse stromal cells; however, the exact timing of the replacement of human with murine stromal cells in human CRC xenograft has not been fully elucidated. We hypothesize that orthologous murine transcripts functionally substitutes for the loss due to replacement of human stromal genes. MATERIALS AND METHODS: Human CRC were implanted in athymic nude mice in replicates and followed-up over time. Using next-generation sequencing, we determined the temporal kinetics of human stromal cell replacement with the orthologous murine transcripts. RESULTS: CRC cell-induced re-organization of the normal, quiescent murine stromal cells into a protumorigenic phenotype supporting human CRC growth occurs at initial implantation. CONCLUSION: Murine cell replacement occurs in a time- and size-dependent manner. Copyright
BACKGROUND/AIM: Patient-derived xenografting (PDX) of humancolorectal cancer (CRC) is the preferred experimental model to study tumor response to therapeutic agents. Gradually, human stromal cells are replaced by mouse stromal cells; however, the exact timing of the replacement of human with murine stromal cells in human CRC xenograft has not been fully elucidated. We hypothesize that orthologous murine transcripts functionally substitutes for the loss due to replacement of human stromal genes. MATERIALS AND METHODS:Human CRC were implanted in athymic nude mice in replicates and followed-up over time. Using next-generation sequencing, we determined the temporal kinetics of human stromal cell replacement with the orthologous murine transcripts. RESULTS: CRC cell-induced re-organization of the normal, quiescent murine stromal cells into a protumorigenic phenotype supporting human CRC growth occurs at initial implantation. CONCLUSION:Murine cell replacement occurs in a time- and size-dependent manner. Copyright
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