title: T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules.
abstract: T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells.
authors.affiliation: Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. LomonosovMoscow State University, Lomonosovsky av., 31/5, Moscow 119192, Russia. rkseniya@mail.ru.
authors.forename: Kseniya A
authors.initials: KA
authors.lastname: Rubina
authors.affiliation: Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. LomonosovMoscow State University, Lomonosovsky av., 31/5, Moscow 119192, Russia. e-semina@yandex.ru.
authors.forename: Ekaterina I
authors.initials: EI
authors.lastname: Surkova
authors.affiliation: Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. LomonosovMoscow State University, Lomonosovsky av., 31/5, Moscow 119192, Russia. e-semina@yandex.ru.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Semina
authors.affiliation: Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. LomonosovMoscow State University, Lomonosovsky av., 31/5, Moscow 119192, Russia. veroniks@mail.ru.
authors.forename: Veronika Y
authors.initials: VY
authors.lastname: Sysoeva
authors.affiliation: Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. LomonosovMoscow State University, Lomonosovsky av., 31/5, Moscow 119192, Russia. n_i_kalinina@mail.ru.
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Kalinina
authors.affiliation: Division of Developmental Neurobiology, MRC National Institute for Medical Research, TheRidgeway, Mill Hill, London NW7 1AA, UK. alexei.poliakov@gmail.com.
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Poliakov
authors.affiliation: Federal State Budgetary Scietific Institution «N.N. Blokhin Russian Cancer Research Center» (FSBSI"N.N.Blokhin RCRC"), Kashirskoe Shosse 24, Moscow 115478, Russia. treshalina@yandex.ru.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Treshalina
authors.affiliation: Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. LomonosovMoscow State University, Lomonosovsky av., 31/5, Moscow 119192, Russia. tkachuk@fbm.msu.ru.
authors.forename: Vsevolod A
authors.initials: VA
authors.lastname: Tkachuk
keywords: T-cadherin; invasion; melanoma; migration