Establishment and maintenance of proper immunity requires a precise balance between cellular adhesion and proliferation. A disruption in either event culminates in a variety of pathologies encompassing immunosuppression, auto immunity, and cancer. Retinoids, profoundly affect immune function by mediating cellular adhesion and proliferation in certain leukocytes. Retinoids, by binding to retinoid receptors (RARs or RXRs), modify the expression of a variety of signaling proteins involved in immune cell proliferation and adhesion including, integrins. Integrins are a family of transmembrane heterodimeric receptors consisting of non-covalently linked α and β subunits that are considered to be the principle receptors involved in attachment to the extracellular matrix and provide adhesive interactions that control cellular proliferation. Currently, the contributions by retinoids in immune cell adhesion and proliferation have been independently examined; however, in retinoid responsive immune cell lines there appears to be a potential synergism between cellular adhesion and proliferation, which may be mediated through integrins, specifically the α5β1 subset. In this study, the effect of all-<i>trans</i>-retinoic acid agonists on K562 cellular adhesion, proliferation, and α5β1 integrin cell surface expression was investigated. RARgamma agonist exposure increased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin and FN-120. Cell surface expression of both the α5 and β1 integrin subunits was increased in the presence of a RARgamma agonist; however, RARgamma agonists decrease K562 cellular proliferation. In the presence of the RARbeta agonist, K562 cellular proliferation was increase, while α5β1 cell surface expression was decreased. The RARalpha agonist was comparable to the control in K562 cellular adhesion, proliferation, and α5β1 integrin cell surface expression. Our study is the first to demonstrate that specific RAR agonists alter cellular adhesion, proliferation, and intergrin cell surface expression.

Effect of retinoid receptor agonists on K562 cellular adhesion, proliferation, and α5β1 integrin cell surface expression

249th National Meeting (2015)

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