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01-11-2019 | Metastasis | Preclinical study

Syndecan-1 facilitates breast cancer metastasis to the brain

Authors: Megan R. Sayyad, Madhavi Puchalapalli, Natasha G. Vergara, Sierra Mosticone Wangensteen, Melvin Moore, Liang Mu, Chevaunne Edwards, Aubree Anderson, Stefanie Kall, Megan Sullivan, Mikhail Dozmorov, Jaime Singh, Michael O. Idowu, Jennifer E. Koblinski

Published in: Breast Cancer Research and Treatment | Issue 1/2019

Abstract

Purpose

Although survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis.

Methods

To assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood–brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 facilitates brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 is silenced.

Results

Silencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that silencing of Sdc1 expression had no effect on attachment of breast cancer cells to brain endothelial cells or astrocytes, but migration across the BBB was reduced as well as adhesion to the perivascular regions of the brain. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines/chemokines, which may influence the BBB.

Conclusions

Taken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

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Title: Syndecan-1 facilitates breast cancer metastasis to the brain
Authors: Megan R. Sayyad
Madhavi Puchalapalli
Natasha G. Vergara
Sierra Mosticone Wangensteen
Melvin Moore
Liang Mu
Chevaunne Edwards
Aubree Anderson
Stefanie Kall
Megan Sullivan
Mikhail Dozmorov
Jaime Singh
Michael O. Idowu
Jennifer E. Koblinski
Publication date: 01-11-2019
Publisher: Springer US
Keywords: Metastasis
Breast Cancer
Breast Cancer
Cytokines
Published in: Breast Cancer Research and Treatment / Issue 1/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05347-0

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