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16. identification and characterization of cancer stem cells in liver cancer    guan xin-yuan
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16. identification and characterization of cancer stem cells in liver cancer guan xin-yuan

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  • 1. Identification and Characterization of Cancer Stem Cells in Hepatocellular Carcinoma Xin-yuan Guan Department of Clinical Oncology The University of Hong Kong
  • 2. Hepatocellular Carcinoma (HCC) HCC 5th most common cancer 3rd leading cause of cancer death  High incidence geographic regions: Southeast Asia, China, sub-Saharan Africa Etiology of HCC  HBV or HCV infection  Aflatoxin B1 intake  Alcohol abuse Obesity, diabetes and nonalcoholic fatty liver disease
  • 3. Tumor-initiating cells (TICs) / Cancer stem cells (CSCs) - CSC has been defined as a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells. - Properties of CSCs – persistent self-renewal, sustained proliferation, tumor initiation. - Other common (but not defining) characteristics of CSCs – rarity within a tumor, stem cell marker expression, ability to differentiate along multiple lineages, chemoresistance, metastasis, etc. - Origin of CSCs – largely unknown. e.g. for leukemia and colon cancer – normal stem cells e.g. for liver cancer – ?
  • 4. Characteristics of CD133+ subpopulation in HCC  CD133+ cells exhibit increased tumorigenic potential  CD133+ cells exhibit an increased potential for self-renewal  CD133+ cells exhibit a marked ability to differentiate  CD133+ cells preferentially express “stemness” genes  CD133+ cells are more resistant to anticancer agents, doxorubicin and 5-fluorouracil
  • 5. Summary Characteristics of CD133+ subpopulations, isolated from HCC clinical specimens and cell lines are consistent with the predicted behavior of cancer stem cells. Ma et al., Gastroenterology 2007 CD133+ CSCs contribute to HCC chemoresistance through activation of the specific Akt/PKB and Bcl-2 survival pathway. Ma et al., Oncogene 2008 Aldehyde dehydrogenase (ALDH) is preferentially expressed in CD133+ cells and can be used to better characterize the CD133+ HCC CSC population. Ma et al., Mole Cancer Res 2008 miR-130b is overexpressed in CD133+ CSCs and regulates tumor growth and selfrenewal via tumor protein TP53-INP1. Ma et al., Cell Stem Cell 2010 CD133+ liver CSCs promote tumor angiogenesis through activation of the NTS / IL-8 / CXCL1 signaling cascade via MAPK signaling. Tang KH, et al. Hepatology 2011 Knowckdown of CD133 can inhibit tumorigenicity of HCC cell lines. Tang KH, et al. Hepatology 2011
  • 6. Acknowledgments Department of Clinical Oncology, HKU Dr. Stephanie Ma Ms. Yangyang Song Ms. Carol Tong Dr. Kwan Ho Tang Dr. Polly Chen Mr. Pak Shing Kwan Department of Surgery, HKU Prof. Chung Mau Lo Dr. Kwan MAN Department of Pathology, HKU Dr. Kwok Wah Chan
  • 7. Thank You Questions or Comments Hong Kong