Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells

Molecular Cancer

Research

Hinke AB Multhaupt¹  John R Couchman¹  Hooi Ching Lim² 

[1] Department of Biomedical Sciences and Biotech Research & Innovation Center, University of Copenhagen, Biocenter, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark;Department of Biomedical Sciences and Biotech Research & Innovation Center, University of Copenhagen, Biocenter, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark;Current address: Stem Cell Center, Lund University, Lund, Sweden;

关键词: Cytoskeleton;    Adhesion;    Syndecan;    Caveolin;    Tumor cells;    Tissue microarray;   

DOI  :  10.1186/s12943-014-0279-8

 received in 2014-07-22, accepted in 2014-12-22,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCell surface proteoglycans interact with numerous regulators of cell behavior through their glycosaminoglycan chains. The syndecan family of transmembrane proteoglycans are virtually ubiquitous cell surface receptors that are implicated in the progression of some tumors, including breast carcinoma. This may derive from their regulation of cell adhesion, but roles for specific syndecans are unresolved.MethodsThe MDA-MB231 human breast carcinoma cell line was exposed to exogenous glycosaminoglycans and changes in cell behavior monitored by western blotting, immunocytochemistry, invasion and collagen degradation assays. Selected receptors including PAR-1 and syndecans were depleted by siRNA treatments to assess cell morphology and behavior. Immunohistochemistry for syndecan-2 and its interacting partner, caveolin-2 was performed on human breast tumor tissue arrays. Two-tailed paired t-test and one-way ANOVA with Tukey’s post-hoc test were used in the analysis of data.ResultsMDA-MB231 cells were shown to be highly sensitive to exogenous heparan sulfate or heparin, promoting increased spreading, focal adhesion and adherens junction formation with concomitantly reduced invasion and matrix degradation. The molecular basis for this effect was revealed to have two components. First, thrombin inhibition contributed to enhanced cell adhesion and reduced invasion. Second, a specific loss of cell surface syndecan-2 was noted. The ensuing junction formation was dependent on syndecan-4, whose role in promoting actin cytoskeletal organization is known. Syndecan-2 interacts with, and may regulate, caveolin-2. Depletion of either molecule had the same adhesion-promoting influence, along with reduced invasion, confirming a role for this complex in maintaining the invasive phenotype of mammary carcinoma cells. Finally, both syndecan-2 and caveolin-2 were upregulated in tissue arrays from breast cancer patients compared to normal mammary tissue. Moreover their expression levels were correlated in triple negative breast cancers.ConclusionCell surface proteoglycans, notably syndecan-2, may be important regulators of breast carcinoma progression through regulation of cytoskeleton, cell adhesion and invasion.

【 授权许可】

Unknown   
© Lim et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.