Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 135, Issue 1, Pages 238-246Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2014.284
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Funding
- Lundbeck foundation, Denmark
- Faculty of Health Sciences, University of Copenhagen
- Novo Nordisk Fonden [NNF12OC0002036] Funding Source: researchfish
- The Danish Cancer Society [R72-A4571] Funding Source: researchfish
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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.
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