Chemotherapy Durg Induces Cancer Stemness And The Identification Of CSC Mouse Model

Part1, Induction of cancer pluripotency by chemotherapy drugRecent studies indicate that cancer stem cells (CSCs) exist in most hematological and solid tumors. CSCs are characterized by their ability to self-renew and their capacity to differentiate into the multitude of cells that comprise the tumor mass. Moreover, these cells have been shown to be intrinsically resistant to conventional anti-cancer therapies. Despite their fundamental role in cancer pathogenesis, the cellular origin, of CSCs remains highly controversial. The aim of this study was to examine whether heterogeneous cancer cells can acquire stem cell-like properties in response to chemotherapy. We demonstrate that carboplatin can induce the self-renewal (spherogenesis) and pluripotency (Sox2and Oct3/4expression) of hepatocellular carcinoma (HCC) cells grown under stem cell culture conditions. Moreover, we show that knockdown of Sox2and Oct3/4gene expression in HCC cells can reduce carboplatin-mediated increases sphere formation. Finally, we show that non-CSC cells, obtained by side population flow cytometric sorting using Hoechst33342, can acquire stem-like properties after exposure to carboplatin. Taken together, our data indicate that bulk cancer cells may be an important source of CSCs during tumor development, and that targeting Sox2and/or Oct3/4may be a promising approach for targeting CSCs in clinical cancer treatment. Part2, Identification animal modle for CSC researchRecent cancer stem cell researches have indicate that those cell plays a irreplaceable role during cancer occur, development, malignant and metastasis. More and more information suggest that the theory of CSC hold many promises for totally cure of cancer. Most of the recent study were done based on primary tumors, cancer cell lines and xenograft mouse model. There are very few report about an animal model specific for CSC research. APCmin/+mouse model is an very excellent and popular model in studying colon cancer for its spontaneous tumor initiation, short breeding cycle, steady phenotype. This study observed all tumors formed in hole intestinal GI track of different aged mice and classify them into small medium and large group. Polyps cell isolation and sphere culture assay result suggest that cancer stem cell in increasing during malignance. Further more, western blotting of whole protein extract from different group of tissue shows that Sox2, Oct4, c-Myc and (3-catenin expression level are elevating by both age and size. This may indicate that cancer stem cells are activating during cancer development. Finally, immuno-chemistry staining of APCmin/+mice whole intestine Swiss roll section also presents the same pattern. This result confirmed our observation form western blotting and provide additional information about location and activation of those sternness gene in APCmin/+tumors. Taken together, our data suggest that cancer stem cell in activating and increase during intestinal cancer development and APCmin/+mouse model can functions as a good cancer stem cell model as well as colon cancer model.