| AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2011;3(4):292-322
Review Article
The emerging importance of α-L-fucose in human breast cancer: a
review
Jay J. Listinsky, Gene P. Siegal, Catherine M. Listinsky
The Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA; The
Department of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
Received May 17, 2011; Accepted July 10, 2011; Epub July 20, 2011; Published August 15, 2011
Abstract: Breast cancer cells incorporate the simple sugar alpha-L-fucose (fucose) into glycoproteins and
glycolipids which, in turn, are expressed as part of the malignant phenotype. We have noted that fucose is not
simply a bystander molecule, but, in fact, contributes to many of the fundamental oncologic properties of breast
cancer cells. Here, we summarize the evidence from us and others that fucose is necessary for key functions of
neoplastic progression including hematogenous metastasis, tumor invasion through extracellular matrices
including basement membranes and up-regulation of the Notch signaling system, with implications for epithelial-
to-mesenchymal transition and activation of breast cancer stem cells. Additionally, certain breast cancer
biomarkers are fucose-rich while a well-known marker of breast cancer progression, soluble E-selectin, is a
known counter-receptor of fucosylated selectin ligands. We provide illustrative examples and supportive
evidence drawn from work with human breast cancer cell lines in vitro as well as clinical studies with human
pathologic material. And finally, we discuss evidence that fucose (or its absence) is central to the mechanisms of
action of several experimental targeted therapies which may prove useful in breast cancer treatment. We
propose that alpha-L-fucose is essential in order to construct first, the malignant and then the metastatic
phenotype of many human breast cancers. This knowledge may inform the search for novel treatment
approaches in breast cancer. (AJTR1105002).
Keywords: Fucose, selectin, biomarker, Notch, trastuzumab, breast cancer
Full Text PDF
Address all correspondence to:
Gene P. Siegal, MD, PhD
Department of Pathology, KB 506
University of Alabama at Birmingham
Birmingham, AL 35233
Phone: (205) 934-6608 Fax: (205) 975-7284
E-mail: gsiegal@uab.edu
Review Article
The emerging importance of α-L-fucose in human breast cancer: a
review
Jay J. Listinsky, Gene P. Siegal, Catherine M. Listinsky
The Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA; The
Department of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
Received May 17, 2011; Accepted July 10, 2011; Epub July 20, 2011; Published August 15, 2011
Abstract: Breast cancer cells incorporate the simple sugar alpha-L-fucose (fucose) into glycoproteins and
glycolipids which, in turn, are expressed as part of the malignant phenotype. We have noted that fucose is not
simply a bystander molecule, but, in fact, contributes to many of the fundamental oncologic properties of breast
cancer cells. Here, we summarize the evidence from us and others that fucose is necessary for key functions of
neoplastic progression including hematogenous metastasis, tumor invasion through extracellular matrices
including basement membranes and up-regulation of the Notch signaling system, with implications for epithelial-
to-mesenchymal transition and activation of breast cancer stem cells. Additionally, certain breast cancer
biomarkers are fucose-rich while a well-known marker of breast cancer progression, soluble E-selectin, is a
known counter-receptor of fucosylated selectin ligands. We provide illustrative examples and supportive
evidence drawn from work with human breast cancer cell lines in vitro as well as clinical studies with human
pathologic material. And finally, we discuss evidence that fucose (or its absence) is central to the mechanisms of
action of several experimental targeted therapies which may prove useful in breast cancer treatment. We
propose that alpha-L-fucose is essential in order to construct first, the malignant and then the metastatic
phenotype of many human breast cancers. This knowledge may inform the search for novel treatment
approaches in breast cancer. (AJTR1105002).
Keywords: Fucose, selectin, biomarker, Notch, trastuzumab, breast cancer
Full Text PDF
Address all correspondence to:
Gene P. Siegal, MD, PhD
Department of Pathology, KB 506
University of Alabama at Birmingham
Birmingham, AL 35233
Phone: (205) 934-6608 Fax: (205) 975-7284
E-mail: gsiegal@uab.edu
 | |  | |  | |  | |  | |  | |  |