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Trends in Cancer Research   Volumes    Volume 7 
Involvement of the plasma membrane-associated S-Gal/CathA/Neu-1 complex in tumor progression
William Hornebeck, Frank Antonicelli
Pages: 75 - 85
Number of pages: 11
Trends in Cancer Research
Volume 7 

Copyright © 2011 Research Trends. All rights reserved

Alteration of the elastic fibers network is one of the characteristics of breast, and lung cancers as well as melanoma. Elastin fragments, i.e. Elastokines, generated by elastases are i) potent chemotactic agents for inflammatory cells, ii) proangiogenic molecules, iii) amplifiers of the invasive phenotype of cancer cells. Those biological effects are mediated mostly by their interaction, at the cell plasma membrane, with an ubiquitously expressed spliced-form of β-galactosidase (S-Gal), linked to neuraminidase-1 (Neu-1) and Cathepsin A. The dual function of S-Gal, together with Neu-1 in directing both elastic fibers assembly and Matrix MetalloProteinases (MMP) expression has been demonstrated in both fibroblasts and smooth muscle cells. MMP up-regulation, following S-Gal occupancy by Elastokines, is observed in all cell types and can be further exacerbated by fibroblast-cancer cells crosstalk. In this setting, Elastokines further engender elastolysis and collagenolysis, thus favoring cancer cells invasion. They can also contribute to elastosis as they are able to i) stimulate tropoelastin synthesis, ii) liberate ROS and RNS recently described as impairing elastic fibers assembly. Finally, elastolysis at a distant organ such as lung might favor the formation of a chemotactic gradient to attract cancer cell in transit.
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