GLI2 shows osteosarcoma treatment promise
MedWire News: Japanese researchers suggest that inhibiting the GLI2 transcription factor could hold promise for treating osteosarcoma, the most common malignant bone tumor in children and adolescents.
Their study showed that GLI2 significantly contributed to the growth of osteosarcoma cells, and that its suppression inhibited growth via cell-cycle regulation.
The team says: "Our findings thus suggest that GLI2 might be an attractive target for therapeutic intervention, particularly in patients with high-grade and/or metastatic osteosarcoma."
GLI2 is a key mediator in the Hedgehog pathway - an organizer of embryonic development whose aberrant activation has been reported in various types of malignant tumors.
Noting that the contribution of GLI2 to neoplasia is poorly understood, Takao Setoguchi (Kagoshima University) and co-workers examined its expression in human osteosarcoma biopsy specimens and found that it was overexpressed in these tissues.
GLI2 knockdown by RNA interference prevented osteosarcoma growth and anchorage-independent growth, the team reports in the Journal of Pathology.
Knockdown of GLI2 promoted the arrest of osteosarcoma cells in the G1 phase of the cell cycle and was accompanied by reduced protein expression of the cell-cycle accelerators cyclin D1, SKP2, and phosphorylated Rb; however, knockdown increased the expression of p21cip1.
Furthermore, forced expression of GLI2 in mesenchymal stem cells promoted their proliferation and accelerated their cell-cycle progression.
Studies in mouse xenograft models also revealed that GLI2 knockdown inhibited the growth of osteosarcoma in nude mice.
The researchers conclude: "Our findings demonstrate that inhibition of GLI2 prevents osteosarcoma growth.
"These findings improve our understanding of osteosarcoma pathogenesis and suggest that inhibition of GLI2 may be regarded as an effective treatment for patients with osteosarcoma."
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By Anita Wilkinson