OPNa overexpression is associated with matrix calcification in thyroid cancer cell lines

Osteopontin (OPN) spliced variants (OPN-SV: OPNa, OPNb, and OPNc) are aberrantly expressed in tumors and frequently associated with cancer progression. This holds true for papillary thyroid carcinoma (PTC), which is the most common type of thyroid cancer (TC). PTC often presents with desmoplasia and dystrophic calcification, including psammoma bodies (PB). This work aimed to investigate total OPN (tOPN) and OPN-SV expression and their association with the presence of PB in the PTC classical variants (cPTC), as well as the involvement of OPN-SV in matrix calcification of TC cell lines. We found that cPTC samples presenting PB showed higher OPN expression levels. In TC cell lines, OPNa overexpression promotes higher matrix calcification and collagen synthesis when compared to that of clones overexpressing OPNb or OPNc. In response to OPN knockdown, calcification was inhibited, paralleled with the downregulation of calcification markers. In conclusion, our data evidenced that OPN expression is associated with the presence of PB in cPTC samples. Among the OPN-SV, OPNa is the main contributor to matrix calcification in tested TC cells, providing clues to a better understanding on the biology and ethiopathogenesis of the calcification process in TC cells. This study was supported by the CNPq (grant n# 237322/2012-9); by FCT (grants n# SFRH/BD/87887/2012 and SFRH/BD/110617/2015); by FEDER “Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020”; by Operacional Programme for Competitiveness and Internationalization “POCI” (grant n# POCI-01-0145-FEDER-007274); by the “Advancing cancer research: from basic knowledge to application” (grand n# NORTE-01-0145-FEDER-000029); and by the “Projetos Estruturados de I & D & I”, funded by Norte 2020—Programa Operacional Regional do Norte.