Dickkopf 3 Inhibits Invasion and Motility of Saos-2 Osteosarcoma Cells by Modulating the Wnt-β-Catenin Pathway

Bang H. Hoang, Tadahiko Kubo, John H. Healey, Rui Yang, Saminathan S. Nathan, E. Anders Kolb, BethAnne Mazza, Paul A. Meyers, Richard Gorlick

Research output: Contribution to journalArticle

220 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2734-2739
Number of pages6
JournalCancer Research
Volume64
Issue number8
DOIs
StatePublished - Apr 15 2004
Externally publishedYes

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Catenins
Wnt Signaling Pathway
Osteosarcoma
Wnt Receptors
Neoplasm Metastasis
Drug Therapy
Starvation
Cell Adhesion
Cell Movement
Transfection
Neoplasms
Apoptosis
Phenotype
Bone and Bones
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dickkopf 3 Inhibits Invasion and Motility of Saos-2 Osteosarcoma Cells by Modulating the Wnt-β-Catenin Pathway. / Hoang, Bang H.; Kubo, Tadahiko; Healey, John H.; Yang, Rui; Nathan, Saminathan S.; Kolb, E. Anders; Mazza, BethAnne; Meyers, Paul A.; Gorlick, Richard.

In: Cancer Research, Vol. 64, No. 8, 15.04.2004, p. 2734-2739.

Research output: Contribution to journalArticle

Hoang, Bang H. ; Kubo, Tadahiko ; Healey, John H. ; Yang, Rui ; Nathan, Saminathan S. ; Kolb, E. Anders ; Mazza, BethAnne ; Meyers, Paul A. ; Gorlick, Richard. / Dickkopf 3 Inhibits Invasion and Motility of Saos-2 Osteosarcoma Cells by Modulating the Wnt-β-Catenin Pathway. In: Cancer Research. 2004 ; Vol. 64, No. 8. pp. 2734-2739.
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