Tenascin C interacts with Ecto-5′-nucleotidase (eN) and regulates adenosine generation in cancer cells

详细信息    查看全文

• 作者：Rafal Sadej ; Kunihiro Inai ; Zenon Rajfur ; Anna Ostapkowicz ; Jon Kohler ; Andrzej C. Skladanowski ; Beverly S. Mitchell ; Jozef Spychala
• 关键词：Ecto-5′ ; -nucleotidase ; CD73 ; Adenosine ; Breast cancer ; Extracellular matrix ; Tenascin C ; Cell adhesion ; Cell motility ; Invasion
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Basis of Disease
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：1782
• 期：1
• 页码：35-40
• 全文大小：365 K

文摘

Tenascin C is expressed in invasive human solid tumors; however its specific role in cancer biology remains obscure. Previously, we have found that ecto-5′-nucleotidase (eN) is a marker of ER (−) breast carcinoma and elevated expression correlates with invasive mesenchymal cell phenotype. To investigate for the potential relationship between eN and protein components of the extracellular matrix (ECM) we measured adenosine generation from AMP in cells incubated with soluble ECM proteins. We found that tenascin C was the only ECM component that strongly inhibited ecto-5′-nucleotidase (eN) activity in situ and adenosine generation from AMP (75 % inhibition, p < 0.01). The inhibition was comparable to that induced by concanavalin A, a well-defined and strong inhibitor of eN. Resin immobilized tenascin C, but not collagen, and only weakly fibronectin, specifically and quantitatively bound cell-extracted eN. We further developed breast cancer cell line with reduced eN expression and tested changes in cell adhesion on different ECM. Breast cancer cells expressing reduced eN attached 56 % weaker (p < 0.05) to immobilized tenascin C. This difference was not detected with other ECM proteins. Finally, control breast cancer cells migrated slower on tenascin C when compared with clone with reduced eN expression. These data suggest that eN is a novel and specific receptor for tenascin C and that the interaction between these proteins may influence cell adhesion and migration and also lead to decreased generation of local adenosine.