SECRETED OSTEOPONTIN-A MEDIATE ANAPLASIC THYROID CARCINOMA PROGRESSION FEATURES BY αVβ3 INTEGRIN RECEPTOR

INTRODUCTION AND OBJECTIVES: Thyroid cancer (TC) is the most frequent endocrine neoplasm worldwide, representing 3% of all estimated tumors. The anaplastic thyroid carcinoma (ATC) is one of the least frequent among the TC subtypes. ATC presents rapid tumor progression and high metastatic rates, reflecting a poor prognosis. Osteopontin (OPN) is a multifunctional protein able to activate tumor progression-related pathways in several tumor types, including TC. Previous studies from our group indicated that OPNa splicing variant is overexpressed inducing progression features in thyroid tumors, including in ATC cell lines. However, the molecular mechanisms by which OPNa promote these effects are still poorly understood. This study aimed to investigate whether integrin and/or CD44 receptors can mediate OPNa effects on distinct aspects related to tumor progression. MATERIAL AND METHODS: The expression of αvβ3 integrin and CD44 surface receptors was evaluated by flow cytometry in the representative ATC cell line, 8505c, which stably overexpress OPNa (8505c-OPNa cells). OPN levels secreted into the conditioned medium (CM) from 8505c-OPNa cells was quantified by ELISA assays. The wild-type 8505c cell line was tested for cell growth, migration and invasion rates in response to culturing in the presence of CM secreted by 8505c-OPNa cells. RESULTS AND CONCLUSION: The expression of αvβ3 integrin was detected on the 8505c-OPNa cell surface, while no CD44 expression was observed. However, αvβ3 integrin expression was not increased in 8505c-OPNa cells when compared to control cells. We also found that CM enriched with secreted OPNa stimulated cell growth, migration and invasion of 8505c wild type cells. Notably, the neutralization of the αvβ3 receptor using an anti- αvβ3 integrin specific antibody inhibited the invasive potential of these cells. Taken together, these findings support that OPNa secreted by the 8505c-OPNa ATC cell line may impact on key functional aspects of ATC progression and that cell invasion could be mediated by the αvβ3 integrin receptor.