Syndecan-1 facilitates breast cancer metastasis to the brain

作者：Megan Sayyad, Madhavi Puchalapalli, Natasha Gupta Vergara, Sierra Mosticone Wangensteen, M. R. Moore, Liang Mu, Chevaunne Edwards, Aubree Anderson, Stefanie L. Kall, Megan Sullivan, Mikhail G. Dozmorov, Jaime A. Singh, Michael O. Idowu, Jennifer E. Koblinski · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2019 · DOI：10.1101/565648 · 被引用次数：8 · 研究领域：Cancer Cells and Metastasis、Proteoglycans and glycosaminoglycans research、Caveolin-1 and cellular processes

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 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 was 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 the reduction in brain metastases with Sdc1 knockdown was likely due to reduced breast cancer cell migration across the BBB and adhesion to the perivascular regions of the brain. However, there was no change in attachment to brain endothelial cells or astrocytes. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines, which ...