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20 - World Journal of Gastroenterology

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Online Submissions: http://www.wjgnet.com/esps/wjg@wjgnet.comdoi:10.3748/wjg.v19.i<strong>20</strong>.2997<strong>World</strong> J Gastroenterol <strong>20</strong>13 May 28; 19(<strong>20</strong>): 2997-3006ISSN 1007-9327 (print) ISSN 2219-2840 (online)© <strong>20</strong>13 Baishideng. All rights reserved.REVIEWColon cancer stem cells: Controversies and perspectivesMaria Ausiliatrice Puglisi, Valentina Tesori, Wanda Lattanzi, Giovanni Battista Gasbarrini, Antonio GasbarriniMaria Ausiliatrice Puglisi, Valentina Tesori, Antonio Gasbarrini,Department <strong>of</strong> Internal Medicine and <strong>Gastroenterology</strong>, GemelliHospital, 00168 Rome, ItalyWanda Lattanzi, Institute <strong>of</strong> Anatomy and Cell Biology, UniversitàCattolica del Sacro Cuore, 00168 Rome, ItalyGiovanni Battista Gasbarrini, Fondazione Ricerca in MedicinaONLUS, 40123 Bologna, ItalyAuthor contributions: Puglisi MA and Tesori V contributedequally to this work; Puglisi MA, Tesori V and Gasbarrini A contributedto the article design, writing and revision; Lattanzi W andGasbarrini GB contributed to the literature research and revision;all authors approved the version to be published.Correspondence to: Maria Ausiliatrice Puglisi, PhD, Department<strong>of</strong> Internal Medicine and <strong>Gastroenterology</strong>, Gemelli Hospital,Largo A. Gemelli 8, 00197 Rome,Italy. ausiliapuglisi@yahoo.itTelephone: +39-6-30156018 Fax: +39-6-30157249Received: January 12, <strong>20</strong>13 Revised: March 25, <strong>20</strong>13Accepted: April 3, <strong>20</strong>13Published online: May 28, <strong>20</strong>13Core tip: According to the “cancer stem cell” (CSC) theory,tumor growth and spread are driven by a minority<strong>of</strong> cancer cells which exhibit characteristics similar tonormal stem cells. Although CSCs have been implicatedin colon carcinogenesis, due to the complexity <strong>of</strong> theirbiology and unsolved technical issues, an unequivocallyapproved identification and isolation strategy is still amatter <strong>of</strong> debate. Several markers have been used toidentify colon CSCs but the function <strong>of</strong> these proteinsin CSC biology has not yet been clarified. Moreover, thepossibility that CSCs might contribute to the failure <strong>of</strong>existing chemotherapies to eradicate malignant tumors,indicate that targeting <strong>of</strong> CSCs may represent a promisingstrategy to eradicate chemoresistant cancers. Aim<strong>of</strong> this review was to acquire more information on thebiology <strong>of</strong> human colon CSCs and shed light on the role<strong>of</strong> this cells in the onset and the maintenance <strong>of</strong> coloncancer.AbstractTumors have long been viewed as a population inwhich all cells have the equal propensity to form newtumors, the so called conventional stochastic model.The cutting-edge theory on tumor origin and progression,tends to consider cancer as a stem cell disease.Stem cells are actively involved in the onset andmaintenance <strong>of</strong> colon cancer. This review is intendedto examine the state <strong>of</strong> the art on colon cancer stemcells (CSCs), with regard to the recent achievements <strong>of</strong>basic research and to the corresponding translationalconsequences. Specific prominence is given to thehypothesized origin <strong>of</strong> CSCs and to the methods fortheir identification. The growing understanding <strong>of</strong> CSCbiology is driving the optimization <strong>of</strong> novel anti-cancertargeted drugs.© <strong>20</strong>13 Baishideng. All rights reserved.Key words: Colon cancer stem cells; Colorectal cancer;CD133; Therapy; ChemoresistancePuglisi MA, Tesori V, Lattanzi W, Gasbarrini GB, Gasbarrini A.Colon cancer stem cells: Controversies and perspectives. <strong>World</strong>J Gastroenterol <strong>20</strong>13; 19(<strong>20</strong>): 2997-3006 Available from: URL:http://www.wjgnet.com/1007-9327/full/v19/i<strong>20</strong>/2997.htm DOI:http://dx.doi.org/10.3748/wjg.v19.i<strong>20</strong>.2997INTRODUCTIONThe intestine epithelium is subjected to a rapid and continuousregeneration, supported by crypt intestinal stemcells (ISCs). This feature severely increases the risk formalignant conversion [1] . Indeed, colorectal cancer (CRC)is one <strong>of</strong> the most common type <strong>of</strong> neoplasm worldwide,representing the second leading cause <strong>of</strong> morbidityand mortality from cancer in both Europe and the UnitedStates. This means that CRC can also be considered one<strong>of</strong> the main national emergencies, both in terms <strong>of</strong> morbidityand in terms <strong>of</strong> social and economic costs [2] .Studies on CRC pathogenesis have been originallyfocusing on the clonal selection process, a model <strong>of</strong> carcinogenesispostulated in 1975 [3] . The characterizationWJG|www.wjgnet.com2997 May 28, <strong>20</strong>13|Volume 19|Issue <strong>20</strong>|

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