Document Detail

Glycomechanics of the metastatic cascade: tumor cell-endothelial cell interactions in the circulation.
MedLine Citation:
PMID:  22101756     Owner:  NLM     Status:  MEDLINE    
Hydrodynamic shear force plays an important role in the leukocyte adhesion cascade that involves the tethering and rolling of cells along the endothelial layer, their firm adhesion or arrest, and their extravasation or escape from the circulatory system by inducing passive deformation, or cell flattening, and microvilli stretching, as well as regulating the expression, distribution, and conformation of adhesion molecules on leukocytes and the endothelial layer. Similarly, the dissemination of circulating tumor cells (CTCs) from the primary tumor sites is believed to involve tethering, rolling, and firm adhesion steps before their eventual extravasation which leads to secondary tumor sites (metastasis). Of particular importance to both the leukocyte adhesion cascade and the extravasation of CTCs, glycoproteins are involved in all three steps (capture, rolling, and firm adhesion) and consist of a variety of important selectin ligands. This review article provides an overview of glycoprotein glycosylation associated with the abnormal glycan expression on cancer cell surfaces, where well-established and novel selectin ligands that are cancer related are discussed. An overview of computational approaches on the effects of fluid mechanical force on glycoprotein mediated cancer cell rolling and adhesion is presented with a highlight of recent flow-based and selectin-mediated cell capturing/enriching devices. Finally, as an important branch of the glycoprotein family, mucins, specifically MUC1, are discussed in the context of their aberrant expression on cancer cells and their role as cancer cell adhesion molecules. Since metastasis relies heavily on glycoprotein interactions in the bloodstream where the fluid shear stress highly regulates cell adhesion forces, it is important to study and understand the glycomechanics of all relevant glycoproteins (well-established and novel) as they relate to the metastatic cascade.
Yue Geng; Jocelyn R Marshall; Michael R King
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review     Date:  2011-11-19
Journal Detail:
Title:  Annals of biomedical engineering     Volume:  40     ISSN:  1573-9686     ISO Abbreviation:  Ann Biomed Eng     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-23     Completed Date:  2012-07-16     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  0361512     Medline TA:  Ann Biomed Eng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  790-805     Citation Subset:  IM    
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
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MeSH Terms
Cell Adhesion
Cell Adhesion Molecules / biosynthesis
Cell Communication*
Endothelial Cells / metabolism*,  pathology
Gene Expression Regulation, Neoplastic*
Mucin-1 / biosynthesis*
Neoplastic Cells, Circulating / metabolism*,  pathology
Transendothelial and Transepithelial Migration*
Grant Support
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/MUC1 protein, human; 0/Mucin-1

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