title: Malignant T cells secrete galectins and induce epidermal hyperproliferation and disorganized stratification in a skin model of cutaneous T-cell lymphoma.
abstract: Cutaneous T-cell lymphomas (CTCLs) are the most common primary skin lymphomas, which are characterized by an accumulation of malignant T cells in the skin. The early lesion resembles both clinically and histologically benign inflammatory disorders and also presents with hyperproliferative epidermis and T-cell infiltration. Despite considerable progress in understanding the molecular mechanisms involved in the malignant transformation of T cells, the causes of the morphological and histopathological features of the disease are largely unknown. We used an organotypic model of CTCL to show that malignant T cells through the secretion of galectin-1 and -3 stimulate vigorous growth of keratinocytes. In parallel, malignant T cells induce disorganized keratinocyte stratification, resembling the early hyperproliferative stage of CTCL. We also observed a loss of attachment between the epithelial and mesenchymal compartments. In addition, hyperproliferation was followed by a downregulation of differentiation markers, such as keratin 10 and involucrin, and a decrease in barrier formation. In conclusion, we provide evidence that malignant T cells orchestrate the histopathological epidermal changes seen in CTCL.
authors.affiliation: Department of Oral Medicine and Pathology, School of Dentistry, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christenze
authors.initials: C
authors.lastname: Thode
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.affiliation: Copenhagen Center for Glycomics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wandall
authors.affiliation: Copenhagen Center for Glycomics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carlsson
authors.affiliation: Department of Biomedical Sciences/CFIM, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.affiliation: Tumorbiologisches Forschungslabor, Würzburg, Germany.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Kauczok
authors.affiliation: Tumorbiologisches Forschungslabor, Würzburg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Wobser
authors.affiliation: Bodylift Center, Virum, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Printzlau
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Ødum
authors.affiliation: Department of Oral Medicine and Pathology, School of Dentistry, University of Copenhagen, Copenhagen, Denmark. Electronic address: sdab@sund.ku.dk.
authors.forename: Sally
authors.initials: S
authors.lastname: Dabelsteen
mesh_terms: D000818:Animals; D001798:Blood Proteins; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D037161:Galectins; D064593:Heterografts; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism* / Q000473:pathology*; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; C445499:LGALS1 protein, human; C428445:LGALS3 protein, human; D011994:Recombinant Proteins