Gla-rich protein is a potential new vitamin K target in cancer: evidences for a direct GRP-mineral interaction.

Autor: Viegas CS; Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal ; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal., Herfs M; VitaK, Maastricht University, 6229 EV Maastricht, The Netherlands., Rafael MS; Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal., Enriquez JL; Algarve Medical Centre, Department of Histopathology, 8000-386 Faro, Portugal., Teixeira A; Algarve Medical Centre, Department of Histopathology, 8000-386 Faro, Portugal., Luís IM; Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal., van 't Hoofd CM; VitaK, Maastricht University, 6229 EV Maastricht, The Netherlands., João A; Lisbon Central Hospital-CHLC, Department of Dermatology, 1169-050 Lisbon, Portugal., Maria VL; Administração Regional de Saúde do Algarve, 8135-014 Faro, Portugal., Cavaco S; Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal., Ferreira A; Lisbon Central Hospital-CHLC, Department of Dermatology, 1169-050 Lisbon, Portugal., Serra M; Private Hospitals of Portugal, HPP-Santa Maria Hospital, 8000-140 Faro, Portugal., Theuwissen E; VitaK, Maastricht University, 6229 EV Maastricht, The Netherlands., Vermeer C; VitaK, Maastricht University, 6229 EV Maastricht, The Netherlands., Simes DC; Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal ; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), University of Algarve, 8005-139 Faro, Portugal.
Jazyk: angličtina
Zdroj: BioMed research international [Biomed Res Int] 2014; Vol. 2014, pp. 340216. Date of Electronic Publication: 2014 May 18.
DOI: 10.1155/2014/340216
Abstrakt: Gla-rich protein (GRP) was described in sturgeon as a new vitamin-K-dependent protein (VKDP) with a high density of Gla residues and associated with ectopic calcifications in humans. Although VKDPs function has been related with γ-carboxylation, the Gla status of GRP in humans is still unknown. Here, we investigated the expression of recently identified GRP spliced transcripts, the γ-carboxylation status, and its association with ectopic calcifications, in skin basal cell and breast carcinomas. GRP-F1 was identified as the predominant splice variant expressed in healthy and cancer tissues. Patterns of γ-carboxylated GRP (cGRP)/undercarboxylated GRP (ucGRP) accumulation in healthy and cancer tissues were determined by immunohistochemistry, using newly developed conformation-specific antibodies. Both GRP protein forms were found colocalized in healthy tissues, while ucGRP was the predominant form associated with tumor cells. Both cGRP and ucGRP found at sites of microcalcifications were shown to have in vitro calcium mineral-binding capacity. The decreased levels of cGRP and predominance of ucGRP in tumor cells suggest that GRP may represent a new target for the anticancer potential of vitamin K. Also, the direct interaction of cGRP and ucGRP with BCP crystals provides a possible mechanism explaining GRP association with pathological mineralization.
Databáze: MEDLINE
Externí odkaz: