title: Loss of LSR affects epithelial barrier integrity and tumor xenograft growth of CaCo-2 cells.
abstract: The lipolysis-stimulated lipoprotein receptor (LSR) is a lipoprotein receptor, serves as host receptor for clostridial iota-like toxins and is involved in the formation of tricellular contacts. Of particular interest is the role of LSR in progression of various cancers. Here we aimed to study the tumor growth of LSR-deficient colon carcinoma-derived cell lines HCT116 and CaCo-2 in a mouse xenograft model. Whereas knockout of LSR had no effect on tumor growth of HCT116 cells, we observed that CaCo-2 LSR knockout tumors grew to a smaller size than their wild-type counterparts. Histological analysis revealed increased apoptotic and necrotic cell death in a tumor originating from LSR-deficient CaCo-2 cells. LSR-deficient CaCo-2 cells exhibited increased cell proliferation in vitro and an altered epithelial morphology with impaired targeting of tricellulin to tricellular contacts. In addition, loss of LSR reduced the transepithelial electrical resistance of CaCo-2 cell monolayers and increased permeability for small molecules. Moreover, LSR-deficient CaCo-2 cells formed larger cysts in 3D culture than their wild-type counterparts. Our study provides evidence that LSR affects epithelial morphology and barrier formation in CaCo-2 cells and examines for the first time the effects of LSR deficiency on the tumor growth properties of colon carcinoma-derived cell lines.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University (ALU), Freiburg, Germany.
authors.forename: Bernd A
authors.initials: BA
authors.lastname: Czulkies
authors.affiliation: Department of Hematology and Oncology, University Medical Center, ALU, Freiburg, Germany.
authors.forename: Justin
authors.initials: J
authors.lastname: Mastroianni
authors.affiliation: Department of Pathology, University Medical Center, ALU, Freiburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lutz
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University (ALU), Freiburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lang
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University (ALU), Freiburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwan
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University (ALU), Freiburg, Germany.
authors.forename: Gudula
authors.initials: G
authors.lastname: Schmidt
authors.affiliation: Department of Pathology, University Medical Center, ALU, Freiburg, Germany.|German Consortium for Translational Cancer Research (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.|Centre for Biological Signalling Studies (BIOSS), ALU, Freiburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Lassmann
authors.affiliation: Department of Hematology and Oncology, University Medical Center, ALU, Freiburg, Germany.|Centre for Biological Signalling Studies (BIOSS), ALU, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University (ALU), Freiburg, Germany.|Centre for Biological Signalling Studies (BIOSS), ALU, Freiburg, Germany.|Freiburg Institute for Advanced Studies (FRIAS), ALU, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University (ALU), Freiburg, Germany.|Present address: Institute of Pharmaceutical Biotechnology. University of Ulm, Ulm, Germany.|Present address: Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papatheodorou
mesh_terms: D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism*; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: D018110:Receptors, Lipoprotein
keywords: cell morphology; cell-cell contact; epithelial barrier; tumor growth; xenograft