期刊
MOLECULAR THERAPY
卷 23, 期 6, 页码 1044-1054出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2015.45
关键词
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资金
- Department of Defense [W81XWH-11-1-0238]
- National Institutes of Health [1R01CA160271-01A1]
- American Cancer Society [IRG-08-060-04]
- Pennsylvania Breast Cancer Coalition
- [U54CA151668]
Shear-resistant adhesion and extravasation of disseminated cancer cells at the target organ is a crucial step in hematogenous metastasis. We found that the vascular adhesion molecule E-selectin preferentially promoted the shear-resistant adhesion and transendothelial migration of the estrogen receptor (ER)-/CD44(+)-hormone-independent breast cancer cells, but not of the ER+/CD44(-)/low-hormone-dependent breast cancer cells. Coincidentally, CD44(+) breast cancer cells were abundant in metastatic lung and brain lesions in ER- breast cancer, suggesting that E-selectin supports hematogenous metastasis of ER-/CD44(+) breast cancer. In an attempt to prevent hematogenous metastasis through the inhibition of a shear-resistant adhesion of CD44(+) cancer cells to E-selectin-expressing blood vessels on the premetastatic niche, an E-selectin targeted aptamer (ESTA) was developed. We demonstrated that a single intravenous injection of ESTA reduced metastases to a baseline level in both syngeneic and xenogeneic forced breast cancer metastasis models without relocating the site of metastasis. The effect of ESTA was absent in E-selectin knockout mice, suggesting that E-selectin is a molecular target of ESTA. Our data highlight the potential application of an E-selectin antagonist for the prevention of hematogenous metastasis of ER-/CD44(+) breast cancer.
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