Syndecan-1 mediates breast cancer metastasis to the brain through IL-8 and PECAM-1 signaling

摘要: Brain metastasis is a devastating, late-stage event affecting approximately 10-30% of breast cancer patients. However, it is not well understood how breast cancer cells migrate across the blood-brain barrier (BBB) and invade into the brain. Syndecans (Sdcs) are cell surface heparan sulfate proteoglycans (HSPGs) that have previously been linked to breast cancer progression and metastasis. Preliminary findings from our lab indicate that Sdc1 may be involved in breast cancer metastasis to the brain. In clinical samples from breast cancer patients with brain metastases, 67% of the brain metastasis samples stained positive for Sdc1 expression. In an experimental mouse model of metastasis, we found that silencing expression of Sdc1 in MDA-231 breast cancer cells greatly reduced metastasis specifically to the brain, with no difference in lung or bone metastases. Additionally, silencing expression of Sdc1 in MDA-231 …