title: Inducible expression and pathophysiologic functions of T-plastin in cutaneous T-cell lymphoma.
abstract: A molecular feature of Sézary syndrome (SS) is the abnormal expression of T-plastin by malignant T cells. Herein, we investigated the molecular mechanisms involved in T-plastin synthesis and the functions of this actin-binding protein, with a special interest in chemoresistance and migration. We confirm the specific expression of T-plastin in peripheral blood lymphocytes (PBLs) from SS patients and its total absence in PBLs from patients with mycosis fungoides, inflammatory cutaneous or hematologic diseases, and from healthy volunteers. Only 3 of 4 SS patients did constitutively express T-plastin. To assess whether T-plastin expression was inducible, T-plastin-negative PBLs were stimulated by phorbol 12-myristate 13-acetate and ionomycin. Our results demonstrate that T-plastin synthesis was induced in negative PBLs from SS patients, other studied patients, and healthy volunteers. Both constitutive and calcium-induced T-plastin expression was down-regulated by calcineurin inhibitors and involved nuclear factor of activated T cells transcription pathway. Constitutive T-plastin expression in SS was associated with resistance to etoposide-induced apoptosis and cell migration toward chemokines (TARC/CCL17, IP-10). In conclusion, T-plastin is a marker restricted to malignant lymphocytes from SS patients and plays a role for cell survival and migration. This opens new strategies for the treatment of SS advanced stages.
authors.affiliation: Centre de Recherche sur la Peau, Université Paris Diderot, Hôpital Saint-Louis, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bégué
authors.forename: Francette
authors.initials: F
authors.lastname: Jean-Louis
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jauliac
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Liliane
authors.initials: L
authors.lastname: Laroche
authors.forename: Nathalie
authors.initials: N
authors.lastname: Parquet
authors.forename: Hervé
authors.initials: H
authors.lastname: Bachelez
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Gilles
authors.initials: G
authors.lastname: Courtois
authors.forename: Laurence
authors.initials: L
authors.lastname: Michel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000378:metabolism; D012751:Sezary Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D050778:NFATC Transcription Factors; C026742:plastin; D019703:Calcineurin; D002118:Calcium