ABSTRACT
The function of Snail2 in mesenchymal tumors is, to date unknown. Using knockdown and overexpression studies, we show that Snail2 regulates migration and invasion of osteosarcoma cells. Knockdown resulted in significantly decreased motility, remodelling of the actin cytoskeleton, and loss of cellular protrusions. Over-expression increased motility, formation of actin-rich cellular protrusions, and altered expression of some non-canonical Wnt pathway components whilst decreasing expression of the adhesion molecule OB-cadherin. Unexpectedly, knockdown also resulted in significantly smaller tumors in an in vivo CAM assay. Therefore Snail2 may be a potential therapeutic target for clinical intervention of osteosarcoma.
Subject(s)
Actin Cytoskeleton/metabolism , Bone Neoplasms/pathology , Osteosarcoma/pathology , Transcription Factors/metabolism , Animals , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Cadherins/genetics , Cell Line, Tumor , Cell Movement , Chick Embryo , Focal Adhesions/metabolism , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Membrane Proteins/genetics , Osteosarcoma/genetics , Osteosarcoma/metabolism , Proto-Oncogene Proteins/genetics , RNA, Small Interfering , Snail Family Transcription Factors , Transcription Factors/genetics , Wnt Proteins/genetics , Wnt-5a ProteinABSTRACT
Snail2 is a marker of malignancy in epithelial tumours; however, in sarcomas, it is not known if this protein is present. Here we examine the expression of Snail2 in one type of sarcoma, osteosarcoma, and explore its relationship to tumour grade, subtype and anatomical location in cases of long bone and cranial bone osteosarcoma. Long bone osteosarcomas typically have a much greater metastatic capability and a poorer prognosis. We find that Snail2 is expressed in the three main subtypes of long bone osteosarcoma--osteoblastic, chondroblastic and fibroblastic. Regression analysis showed that Snail 2 expression was statistically correlated with tumour grade (p = 0.014) in all of these subtypes. Snail2 was only expressed in high-grade cranial bone osteosarcomas, suggesting a link between Snail2 expression and metastasis. This is the first time Snail2 has been associated with any sarcoma, and this study shows that Snail2 may be a useful prognostic marker for this disease.
