Gla-Rich Protein Is a Potential New Vitamin K Target in Cancer: Evidences for a Direct GRP-Mineral Interaction
| Autor: | Vera L. Maria, Inês M. Luís, Dina C. Simes, Cees Vermeer, Marjolein Herfs, Marta S. Rafael, Cynthia van 't Hoofd, Ana Ferreira, Alexandra Teixeira, Manuel Serra, José L. Enriquez, Carla Viegas, Alexandre João, Sofia Cavaco, Elke Theuwissen |
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| Přispěvatelé: | Promovendi NTM, RS: CARIM - R1 - Thrombosis and haemostasis, Biochemie |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Skin Neoplasms Vitamin K Article Subject Osteocalcin lcsh:Medicine chemistry.chemical_element Breast Neoplasms Calcitonin gene-related peptide Calcium Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans 030304 developmental biology 0303 health sciences Alpha-galactosidase General Immunology and Microbiology lcsh:R Alternative splicing Calcinosis General Medicine In vitro Endocrinology chemistry Carcinoma Basal Cell 030220 oncology & carcinogenesis alpha-Galactosidase Cancer research biology.protein Immunohistochemistry Female Antibody hormones hormone substitutes and hormone antagonists Research Article Naphthoquinones |
| Zdroj: | BioMed Research International. Hindawi Publishing Corporation BioMed Research International BioMed Research International, Vol 2014 (2014) |
| ISSN: | 2314-6133 |
| Popis: | 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 withγ-carboxylation, the Gla status of GRP in humans is still unknown. Here, we investigated the expression of recently identified GRP spliced transcripts, theγ-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 ofγ-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 havein vitrocalcium 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: | OpenAIRE |
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