cxcr4 mediated chemotaxis is regulated by 5t4 oncofetal glycoprotein in mouse embryonic cells趋化因子受体cxcr4介导趋化性是由5 t4在老鼠胚胎细胞瘤胎糖蛋白.pdfVIP

CXCR4 Mediated Chemotaxis Is Regulated by 5T4 Oncofetal Glycoprotein in Mouse Embryonic Cells 1 1 1 1,2 Thomas D. Southgate , Owen J. McGinn , Fernanda V. Castro , Andrzej J. Rutkowski , Mariam 1 1 1,2 1 1 Al-Muftah , Georgi Marinov , Graeme J. Smethurst , David Shaw , Christopher M. Ward , Crispin J. 2 1 Miller , Peter L. Stern * 1 Immunology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom, 2 Applied Computational Biology and Bioinformatics Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom Abstract 5T4 oncofetal molecules are highly expressed during development and upregulated in cancer while showing only low levels in some adult tissues. Upregulation of 5T4 expression is a marker of loss of pluripotency in the early differentiation of embryonic stem (ES) cells and forms an integrated component of an epithelial-mesenchymal transition, a process important during embryonic development and metastatic spread of epithelial tumors. Investigation of the transcriptional changes in early ES differentiation showed upregulation of CXCL12 and down-regulation of a cell surface protease, CD26, which cleaves this chemokine. CXCL12 binds to the widely expressed CXCR4 and regulates key aspects of development, stem cell motility and tumour metastasis to tissues with high levels of CXCL12. We show that the 5T4 glycoprotein is required for optimal functional cell surface expression of the chemokine receptor CXCR4 and CXC