Data/hora: 13/06/2024 06:32:23

Provedor de dados: | Nature Precedings
País: | United Kingdom
Título: | A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies.
Autores: | Carl Gregory; Narae Lee; Angela Smolarz; Scott Olson; Odile David; Jacob Reiser; Robert Kutner; Najat Daw; Darwin Prockop; Edwin Horwitz.
Data: | 2007-06-20
Ano: | 2007
Palavras-chave: | Biotechnology; Cancer.
Resumo: | Canonical Wnt signaling is an osteo-inductive signal that promotes bone repair through acceleration of osteogenic differentiation by progenitors. Dkk-1 is a secreted inhibitor of canonical Wnt signaling and thus inhibits osteogenesis. To examine a potential osteo-inhibitory role of Dkk-1 in osteosarcoma (OS), we measured serum Dkk-1 in pediatric patients with OS (median age, 13.4 years) and found it to be significantly elevated. We also found that Dkk-1 was maximally expressed by the OS cells at the tumor periphery and _in vitro_ Dkk-1 and RANKL are co-expressed by rapidly proliferating OS cells. Both Dkk-1 and conditioned media from OS cells reduces osteogenesis by human mesenchymal cells and by immuno-depletion of Dkk-1, or by adding a GSK3[beta] inhibitor, the effects of Dkk-1 were attenuated. In mice, we found that the expression of Dkk-1 from implanted tumors was similar to the human tumor biopsies in that human Dkk-1 was present in the serum of recipient animals. These data demonstrate that systemic levels of Dkk-1 are elevated in osteosarcoma. Furthermore, the expression of Dkk-1 by the OS cells at the periphery of the tumor probably contributes to its expansion by inhibiting repair of the surrounding bone. These data demonstrate that Dkk-1 may serve as a prognostic or diagnostic marker for evaluation of OS and furthermore, immuno-depletion of Dkk-1 or administration of GSK3[beta] inhibitors could represent an adjunct therapy for this disease.
Tipo: | Manuscript

Identificador:

http://precedings.nature.com/documents/130/version/1

oai:nature.com:10101/npre.2007.130.1

http://hdl.handle.net/10101/npre.2007.130.1

Fonte: | Nature Precedings
Fonte: | Creative Commons Attribution 3.0 License