Zhang P et al. – A new invasion and metastasis-regulating pathway in osteosarcoma is reported and a novel function for the Notch pathway is defined: regulation of metastasis; pharmacologic inhibition of the pathway suggests a possible new treatment to reduce invasion and metastasis in osteosarcoma Methods
Study of Notch pathway genes in human osteosarcoma cell lines and samples
Pharmacologic and retroviral manipulation of the Notch pathway
Analysis of the effect of manipulation on osteosarcoma cell proliferation, survival, anchorage-independent growth, invasion, and metastasis in vitro and in vivo
Results
Expression of the Notch pathway genes Notch ligand DLL1, Notch1 and Notch2 and the Notch target gene HES1 in osteosarcoma cells
HES1 expression associated with invasive and metastatic potential
Pathway signaling blockade by a small molecule inhibitor of {gamma} secretase eliminated invasion in Matrigel with no effect on cell proliferation, survival, or anchorage-independent growth
Manipulation of Notch and HES1 signaling critically affects HES1 in osteosarcoma invasiveness and metastasis in vivo
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