We now show in vitro and in vivo that targeted inhibition of the expression of CD44v6 depletes the ability of the colon tumor cells to signal through hyaluronan-CD44v6 interactions. Although the anti-tumor activity of hyaluronan-oligosaccharides, a hyaluronan-CD44 interaction antagonist, is effective in sensitizing tumor cells to chemotherapeutic agents and reducing tumor growth in xenografts, hyaluronan-oligosaccharide alone was not effective in reducing tumor progression in Apc Min/+ mice. Inhibition of the hyaluronan-CD44 interactions on tumor cells by hyaluronan-CD44 interaction antagonists suppresses these activities by disassembling the complex. Our studies have shown that constitutive interactions between hyaluronan and CD44 on tumor cells induces various anti-apoptotic cell survival pathways through the formation of a multimeric signaling complex that contains activated receptor tyrosine kinases.
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