title: Cell surface galectin-3 defines a subset of chemoresistant gastrointestinal tumor-initiating cancer cells with heightened stem cell characteristics.
abstract: Recurrence of gastrointestinal adenocarcinomas after surgery and chemotherapy may be attributed, in part, to the presence of a small population of tumor-initiating cancer stem cells (CSC). The expression of galectin-3 (Gal3), a multifunctional oncolectin, has been associated with biological behaviors associated with CSC. We examined the ability of Gal3 to characterize the CSC phenotype, and to identify a clinically important gastrointestinal cancer CSC population. Human colorectal and pancreatic cancer cell lines were sorted to identify subpopulations expressing commonly used CSC markers, and Gal3-positive CSC subpopulations. The association of Gal3 with the stem cell properties and alterations of these phenotypes by manipulation of Gal3 expression was examined. Gastrointestinal cancer cell lines contain both Gal3-positive and Gal3-negative subpopulations. Gal3-positive CSCs are characterized by high ALDH activity, enhanced self-renewal ability in vitro (sphere formation) and tumor forming ability in vivo, and resistance to chemotherapeutic agents and death-receptor-mediated apoptosis compared to Gal3-negative CSCs. Silencing Gal3 modifies this behavior. Cell surface Gal3 expression identifies a subset of CSCs in gastrointestinal cancers with high levels of stem cell characteristics, including chemoresistance. This may provide a platform for developing treatment strategies that target CSC.
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors: Matthias
authors: M
authors: Ilmer
authors: Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors: Nachman
authors: N
authors: Mazurek
authors: Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors: James C
authors: JC
authors: Byrd
authors: Department of Stem Cell Transplantation and Cellular Therapies, University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors: Karen
authors: K
authors: Ramirez
authors: Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors: Margarete
authors: M
authors: Hafley
authors: Department of Medicine, Tulane University Health Science Center, New Orleans, LA USA.
authors: Eckhard
authors: E
authors: Alt
authors: Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors: Jody
authors: J
authors: Vykoukal
authors: Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors: Robert S
authors: RS
authors: Bresalier
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020868:Gene Silencing; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D037502:Galectin 3