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Galectin-1 Influences Breast Cancer Cell Adhesion to E-selectin Via Ligand Intermediaries

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Abstract

Introduction

Invasion of other tissues during bloodborne metastasis in part requires adhesion of cancer cells to vascular endothelium by specific fluid shear-dependent receptor–ligand interactions. This study investigates the hypothesis that the adhesion is mediated by ligands shared between endothelial E-selectin and Galectin-1 (Gal-1), both of which are upregulated during inflammation and cancer.

Methods

Flow chamber adhesion and dynamic biochemical tissue analysis (DBTA) assays were used to evaluate whether Gal-1 modulates E-selectin adhesive interactions of breast cancer cells and tissues under dynamic flow conditions, while immunocytochemistry, immunohistochemistry, western blotting, and fluorescence anisotropy were used to study molecular interactions under static conditions.

Results

Dynamic adhesion assays revealed a shear-dependent binding interaction between Gal-1hFc treated breast cancer cells and tissues and E-selectin-coated beads, causing ~ 300% binding increase of the beads compared to negative controls. Immunocyto- and immunohistochemical analyses showed that Gal-1 and E-selectin fluorescent signals colocalized on cells and tissues at ~ 75% for each assay. Immunoprecipitation and Western blotting of Mac-2BP from breast cancer cell lysates revealed that Gal-1 and E-selectin share Mac-2BP as a ligand, while fluorescence anisotropy and circulating tumor cell model systems exhibited competitive or antagonistic binding between Gal-1 and E-selectin for shared ligands, including Mac-2BP. Furthermore, Mac-2BP functional blockade inhibited the effects of Gal-1 on E-selectin binding.

Conclusions

In summary, this investigation reveals a shear-dependent interaction between E-selectin and Gal-1 that may be due to intermediation by a similar or shared ligand(s), including Mac-2BP, which may provide a rational basis for development of novel diagnostics or therapeutics for breast cancer.

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Acknowledgments

The authors would like to thank Mr. Alexander Ostermann, Mr. Yinan Huang, and Dr. Grady Carlson (Department of Chemical and Biomolecular Engineering, Ohio University) for their insight and technical expertise. This research was funded in part by National Institutes of Health R15CA161830 (to M.M.B.), National Science Foundation Grant 1039869 (to M.M.B.), and an Ohio University Foundation Board of Trustees 1804 Fund Award (to A.M.F.).

Conflict of interest

Monica Burdick has received research grant R15CA161830 from the National Institutes of Health and Major Research Instrumentation grant 1039869 from the National Science Foundation. Amir Farnoud has received a research grant 1804 Fund Award from the Ohio University Board of Trustees. Nathan Reynolds, Amina Mohammadalipour, Claire Hall, and Ali Asghari Adib declare that they have no conflicts of interest.

Human Studies/Informed Consent

No human studies were carried out by the authors for this article.

Animal Studies

No animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Biomedical Engineering Program, Russ College of Engineering and Technology, Ohio University, Athens, OH, USA

    Nathan M. Reynolds, Ali Asghari Adib, Amir M. Farnoud & Monica M. Burdick

  2. Department of Chemical and Biomolecular Engineering, Russ College of Engineering and Technology, Ohio University, 171 Stocker Center, 1 Ohio University, Athens, OH, 45701, USA

    Amina Mohammadalipour, Claire R. Hall, Amir M. Farnoud & Monica M. Burdick

  3. Translational Biomedical Science Program, The Graduate College, Ohio University, 1 Ohio University, Athens, OH, 45701, USA

    Nathan M. Reynolds, Amir M. Farnoud & Monica M. Burdick

  4. Edison Biotechnology Institute, Ohio University, 1 Ohio University, Athens, OH, 45701, USA

    Monica M. Burdick

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  1. Nathan M. Reynolds
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Correspondence to Monica M. Burdick.

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Associate Editor Michael R. King oversaw the review of this article.

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Reynolds, N.M., Mohammadalipour, A., Hall, C.R. et al. Galectin-1 Influences Breast Cancer Cell Adhesion to E-selectin Via Ligand Intermediaries. Cel. Mol. Bioeng. 11, 37–52 (2018). https://doi.org/10.1007/s12195-017-0512-9

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