title: Retinoids Bias Integrin Expression and Function in Cutaneous T-Cell Lymphoma.
abstract: Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of malignancies characterized by accumulation of malignant T-cells within the skin. Retinoids, metabolic derivatives, and synthetic analogs of vitamin A embody an effective CTCL therapy with over three decades of clinical use. The established mechanism of action is induction of growth arrest and apoptosis. However, the natural role of retinoids in T-cell biology is imprinting gut-homing properties by inducing integrin α4β7 expression. How the natural role of retinoids relates to therapeutic effectiveness in CTCL has not been addressed and merits investigation. Here we provide evidence that retinoids, including Bexarotene, selectively induce CTCL lineages to increase integrin β7 expression and function prior to growth arrest and apoptosis. Interestingly, augmented CTCL cell adhesion obtained with retinoid exposure was potently attenuated by 1,25-dihydroxyvitamin D3, a metabolic vitamin derivative involved in prompting immune cell skin homing. The integrin-dependent adhesion changes in CTCL cells occurred through synergistic activation of RAR and RXR nuclear receptors. These data explore the early cellular changes induced by retinoids that may be pivotal to sensitizing CTCL cells to growth arrest and apoptosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Sebastian S
authors.initials: SS
authors.lastname: DeMarco
authors.affiliation: Department of Biochemistry and Molecular Biology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
authors.forename: JianMing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Dermatology Division, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Phillips
authors.affiliation: Department of Biochemistry and Molecular Biology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA; East Carolina Diabetes and Obesity Institute, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA. Electronic address: bridgesl@ecu.edu.
authors.forename: Lance C
authors.initials: LC
authors.lastname: Bridges
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism* / Q000473:pathology; D012176:Retinoids / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D039641:Integrin beta Chains; D012176:Retinoids; C091368:integrin beta7; D002117:Calcitriol
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