Wnt10b induces chemotaxis of osteosarcoma and correlates with reduced survival.
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.


METHODS
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 beta-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, beta-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.
Chen
Kevin
K
Georgetown University School of Medicine, Washington, District of Columbia, USA.
Fallen
Shannon
S
Abaan
Hatice Ozel
HO
Hayran
Mutlu
M
Gonzalez
Corina
C
Wodajo
Felasfa
F
MacDonald
Tobey
T
Toretsky
Jeffrey A
JA
Uren
Aykut
A
D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D002633:Chemotaxis; D051157:Frizzled Receptors / Q000032:analysis; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology*; D012516:Osteosarcoma / Q000401:mortality / Q000473:pathology*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction; D015996:Survival Rate; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins / Q000032:analysis / Q000502:physiology*; D051176:beta Catenin
D051157:Frizzled Receptors; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; C491119:WNT10B protein, human; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; D051176:beta Catenin