Wnt10b induces chemotaxis of osteosarcoma and correlates with reduced survival
Abstract
Background: Osteosarcoma (OS) is a primary malignant tumor of the bone that typically presents in the second decade of life and has a poor prognosis, especially in metastatic cases. Wnt signaling contributes to the pathogenesis of tumors such as colon cancer and malignant melanoma. Wnt signaling controls normal bone formation during embryogenesis and homeostasis in adult organisms, thus we evaluated Wnt signaling in OS. Procedure: We surveyed the expression of Wnts, their receptors, Frizzleds and LRPs, and soluble Wnt inhibitors (sFRPs) in four OS cell lines by RT‐PCR. We also tested biological response of OS cell lines to exogenous Wnts by measuring β‐catenin stabilization, Dvl phosphorylation, TOPFLASH activity and chemotaxis. Human OS tumor microarrays were evaluated for expression of Wnt10b by immunohistochemistry. Results: All cell lines tested showed expression of at least three Wnts and one Frizzled. Exogenous Wnt3a and Wnt10b treatment induced Dvl phosphorylation, β‐catenin stabilization and TCF4 transcriptional activity in both metastatic and non‐metastatic murine OS cell lines. Metastatic OS cell lines showed better chemotaxis response to Wnts than the non‐metastatic OS cell lines. Immunohistochemistry studies of 44 human OS samples demonstrated that Wnt10b expression correlated with decreased overall survival. Conclusions: These results further supports a possible autocrine or paracrine Wnt pathway in metastatic potential of OS. Pediatr Blood Cancer 2008;51:349–355. © 2008 Wiley‐Liss, Inc.
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Activation of the WNT-β-catenin pathway is important during early steps in the osteosarcoma metastatic cascade.
“Activation of the WNT-β-catenin pathway is important during early steps in the metastatic cascade 70,71 .”
From Osteosarcoma (2022) · cites this paper as [70]
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- Authors
- Chen, K., Fallen, S., Abaan, H. Ö., Hayran, M., Gonzalez, C., Wodajo, F., MacDonald, T., Toretsky, J. A., & Üren, A.
- Affiliations
- Georgetown University (US)
- Hacettepe University (TR)
- Children's National (US)
- Corresponding author
- Üren, Aykut
- ORCID
- Venue
- Pediatric Blood & Cancer
- Publisher
- Wiley
- Published
- 2008-05-08
- Volume
- 51
- Issue
- 3
- Pages
- 349-355
- ISSN
- 1545-5009 (ISSN-L)
- 1545-5017
- OpenAlex
- W2011991737
- Cited by
- 74
- References
- 39
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 6
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Blood & Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA108641, R01CA108641, R01CA088004, CA 88004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- osteosarcoma, Wnt10b, Wnt signaling, chemotaxis, metastasis, β-catenin stabilization, Frizzled receptors, autocrine and paracrine signaling, overall survival, Wnt3a
- MeSH terms
- Animals, Cell Communication, Chemotaxis, Humans, Neoplasm Metastasis, Proto-Oncogene Proteins, Osteosarcoma, Signal Transduction, Survival Rate, Cell Line, Tumor, Wnt Proteins, Frizzled Receptors, beta Catenin, Mice, TCF Transcription Factors, Transcription Factor 7-Like 2 Protein
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