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tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell

World Journal of Gastroenterology 2018年第24期24卷 2567-2581页

作者： Jian-Peng Gao Wei Xu Wen-Tao Liu Min Yan Zheng-Gang Zhu Department of Surgery Shanghai Institute of Digestive SurgeryRuijin HospitalShanghai Jiao Tong University

Gastric cancer(GC) remains one of the most common and malignant types of cancer due to its rapid progression, distant metastasis, and resistance to conventional chemotherapy, although efforts have been made to understand the underlying mechanism of this resistance and to improve clinical outcome. It is well recognized that tumor heterogeneity, a fundamental feature of malignancy, plays an essential role in the cancer development and chemoresistance. The model of tumor-initiating cell(TIC) has been proposed to explain the genetic, histological, and phenotypical heterogeneity of GC. TIC accounts for a minor subpopulation of tumor cells with key characteristics including high tumorigenicity, maintenance of self-renewal potential, giving rise to both tumorigenic and non-tumorigenic cancer cells, and resistance to chemotherapy. Regarding tumor-initiating cell of GC(GATIC), substantial studies have been performed to(1) identify the putative specific cell markers for purification and functional validation of GATICs;(2) trace the origin of GATICs; and(3) decode the regulatory mechanism of GATICs. Furthermore, recent studies demonstrate the plasticity of GATIC and the interaction between GATIC and its surrounding factors(TIC niche or tumor microenvironment). All these investigations pave the way for the development of GATIC-targeted therapy, which is in the phase of preclinical studies and clinical trials. Here, we interpret the heterogeneity of GC from the perspectives of TIC by reviewing the above-mentioned fundamental and clinical studies of GATICs. Problems encountered during the GATIC investigations and the potential solutions are also discussed.

关键词： Gastric cancer tumor heterogeneity tumor-initiating cell

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MiRNAs in hepatic tumor-initiating cells

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Cancer Biology & Medicine 2018年第S1期15卷 13-13页

作者： Junfang Ji Life Sciences Institute Zhejiang UniversityHangzhouChina

Objective:MicroRNAs(miRNAs)have a large number of biologically diverse effects including cell development and ***-initiating cells or cancer stem cells(CSCs)are responsible for tumor initiation,tumor metastasis,and re... 详细信息

关键词： MiRNAs hepatic tumor-initiating

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Matrigel modulates a stem cell phenotype and promotes tumor formation in a mantle cell lymphoma cell line

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Stem Cell Discovery 2013年第3期3卷 167-179页

作者： Abigail Hielscher Timothy McGuire Dennis Weisenburger John Graham Sharp Department of Cell Biology Genetics and Anatomy University of Nebraska Medical Center Omaha USA

tumors may be maintained by subpopulations of cells possessing stem cell-like properties. We evaluated the stem cell-like and tumor-forming properties of side population (SP) and CD133+/ CD44+ cells in Granta 519, a human mantle cell lymphoma cell line. The in-vitro Cobblestone Area Forming Cell (CAFC) assay, designed to detect stem and progenitor cells, revealed that SP cells contained the greatest proportion of stem cell-like cells. The addition of Matrigel to CAFC assays of SP and non-SP cells both increased their respective stem cell frequencies in comparison to those cultures without Matrigel, and additionally resulted in observed stem cell frequencies which were the same between SP and non-SP cells. Contrary, Matrigel decreased the stem cell frequencies of CD133+/CD44+ or CD133-/CD44- cells. In-vivo assays revealed tumor formation from Matrigel-mixed SP and non-SP cells, and in one instance, occurred with as few as one Matrigel-mixed SP cell. Vehicle-mixed injections of SP and non-SP tumor cells resulted in tumor formation from SP cells only. tumor formation did not occur from Matrigel nor hyaluronan (cellular substrate for CD44-expressing cells)-mixed populations of CD133+/CD44+ or CD133-/CD44- cells. These data demonstrate that Matrigel modulates a stem cell phenotype and promotes tumor formation from SP and non-SP cells. The tumor micro-environmental niche and tumor cell to micro-environmental interactions may be important future targets for novel chemotherapeutic agents.

关键词： Mantle Cell Lymphoma Side Population tumor-initiating Cells Microenvironment

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DNA damage and breast cancer

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World Journal of Clinical Oncology 2011年第9期2卷 329-338页

作者： Jennifer D Davis Shiaw-Yih Lin Department of Systems Biology Unit 950The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States

Cancer is intimately related to the accumulation of DNA damage,and repair failures(including mutation prone repair and hyperactive repair systems).This article relates current clinical categories for breast cancer and their common DNA damage repair *** is included on the potential for accumulation of DNA damage in the breast tissue of a woman during her lifetime and the role of DNA damage in breast cancer *** then cover endogenous and exogenous sources of DNA damage,types of DNA damage repair and basic signal transduction pathways for three gene products involved in the DNA damage response system;namely BRCA1,BRIT1 and *** genes are often considered tumor suppressors because of their roles in DNA damage response and some are under clinical investigation as likely sources for effective new drugs to treat breast *** we discuss some of the problems of DNA damage repair systems in cancer and the conundrum of hyper-active repair systems which can introduce mutations and confer a survival advantage to certain types of cancer cells.

关键词： BRCA1 BRIT1 Classification of breast cancer DNA damage PARP-1 Triple-negative breast cancer tumor-initiating cells

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