Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-β-Catenin pathway Journal Article
| Authors: | Hoang, B. H.; Kubo, T.; Healey, J. H.; Yang, R.; Nathan, S. S.; Kolb, E. A.; Mazza, B.; Meyers, P. A.; Gorlick, R. |
| Article Title: | Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-β-Catenin pathway |
| Abstract: | Osteosarcoma (OS) is a primary malignancy of bone with a tendency to metastasize early. Despite intensive chemotherapy and surgical resection, ∼30% of patients still develop distant metastasis. Our previous work using clinical OS samples suggested that expression of the Wnt receptor LRP5 might be associated with tumor metastasis. In the present study, we used a Dickkopf (Dkk) family member and a dominant-negative LRP5 receptor construct to modulate Wnt signaling in OS cells. Saos-2 cells, which ectopically express Dkk-3, do not undergo apoptosis and exhibit enhanced resistance to serum starvation and chemotherapy-induced cytotoxicity. Transfection of Dkk-3 and dominant-negative LRP5 into Saos-2 cells significantly reduces invasion capacity and cell motility. This blockade is associated with changes in cell morphology consistent with a less invasive phenotype. In addition, Dkk-3 and dominant-negative LRP5 also induce changes in β-catenin localization consistent with an increase in cell-cell adhesion. Taken together, these results support a possible role for Wnt signaling in the pathobiology and progression of human OS. |
| Keywords: | osteosarcoma; signal transduction; cancer chemotherapy; controlled study; bone neoplasms; intercellular signaling peptides and proteins; human cell; proto-oncogene proteins; pathogenesis; protein localization; proteins; phenotype; gene; cell structure; apoptosis; cytotoxicity; cell line, tumor; transfection; carcinogenesis; cancer invasion; genetic transfection; cell movement; protein biosynthesis; cytoplasm; neoplasm invasiveness; trans-activators; wnt proteins; beta catenin; cell adhesion; wnt protein; cell motility; serum; osteosarcoma cell; cytoskeletal proteins; cell strain; zebrafish proteins; receptors, ldl; ldl-receptor related proteins; humans; human; priority journal; article; cell strain saos 2; dickkopf 3 gene |
| Journal Title: | Cancer Research |
| Volume: | 64 |
| Issue: | 8 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-04-15 |
| Start Page: | 2734 |
| End Page: | 2739 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-03-1952 |
| PROVIDER: | scopus |
| PUBMED: | 15087387 |
| DOI/URL: | |
| Notes: | Cancer Res. -- Cited By (since 1996):143 -- Export Date: 16 June 2014 -- CODEN: CNREA -- Source: Scopus |
