RT info:eu-repo/semantics/article
T1 Chemical modulation of VLA integrin affinity in human breast cancer cells.
A1 Valenzuela Fernández, Agustín
A1 K. Pec, Martina
A1 Artwohl, Michaela
A1 Fernández, José J.
A1 Souto, María L.
A1 Álvarez de la Rosa, Diego
A1 Giráldez, Teresa
A1 Díaz González, Federico
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral".
K1 VLA-integrins
K1 Adhesion
K1 Extracellular matrix
K1 Collagen
K1 Fibronectin
K1 Integrin activation
K1 Cancer
K1 Apoptosis
K1 Breast cancer cell
K1 Dehydrothyrsiferol
AB The fact that disruption of integrin–extracellular matrix contacts leads to cell death, hasconverted cell adhesion into a potential target for the control of invasive cancer. In thiswork, we studied the functional consequences of the interference with the activity of thevery late activation antigen (VLA) family of integrins in human breast cancer cell lines ofdistinct malignancy. The α2β1-mediated adhesion reduced the entry of highly malignant,hormone-independent breast cancer cells into apoptosis. Adhesion of breast cancer cellsthrough the VLA integrins α2β1 and α5β1 was significantly reduced by an apoptosisinducing natural triterpenoid, dehydrothyrsiferol (DT), when studied on low amounts ofextracellular matrix. This effect was dose-dependent, not related to cell toxicity and notshared with apoptosis-inducing standard chemotherapeutics, such as doxorubicin andtaxol. The compound did not affect either the cell surface expression level of VLA integrinsor cell distribution of vinculin and actin during cell spreading. In addition, neitherphosphorylation of the focal adhesion kinase pp125FAK on Tyr397 nor the protein kinaseB (Akt/PKB) on Ser473 was significantly altered by DT. The integrin activation level, assessedby binding of soluble collagen to the α2β1 integrin, was reduced upon cell treatment withDT. Importantly, the TS2/16, an anti-β1 activating monoclonal antibody was able to rescueDT-treated cells from apoptosis. Since the activation state of integrins is increasinglyrecognized as an essential factor in metastasis formation, findings presented herein revealthat the chemical regulation of integrin affinity may be a potential therapeutic strategy incancer therapy.
YR 2007
FD 2007
LK http://riull.ull.es/xmlui/handle/915/35332
UL http://riull.ull.es/xmlui/handle/915/35332
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DS Repositorio institucional de la Universidad de La Laguna
RD 30-jun-2024