Gla-Rich Protein Is a Potential New Vitamin K Target in Cancer: Evidences for a Direct GRP-Mineral Interaction

摘要: Gla-rich protein (GRP) was described in sturgeon as a new vitamin-K-dependent (VKDP) with high density of Gla residues and associated ectopic calcifications humans. Although VKDPs function has been related γ-carboxylation, the status GRP humans is still unknown. Here, we investigated expression recently identified spliced transcripts, γ-carboxylation status, its association calcifications, skin basal cell breast carcinomas. GRP-F1 predominant splice variant expressed healthy cancer tissues. Patterns γ-carboxylated (cGRP)/undercarboxylated (ucGRP) accumulation tissues were determined by immunohistochemistry, using newly developed conformation-specific antibodies. Both forms found colocalized tissues, while ucGRP form tumor cells. cGRP at sites microcalcifications shown to have vitro calcium mineral-binding capacity. The decreased levels predominance cells suggest that may represent target for anticancer potential vitamin K. Also, direct interaction BCP crystals provides possible mechanism explaining pathological mineralization.