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2015 ; 23
(6
): 1044-1054
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gab.com Text
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Blocking the adhesion cascade at the premetastatic niche for prevention of breast
cancer metastasis
#MMPMID25815697
Kang SA
; Hasan N
; Mann AP
; Zheng W
; Zhao L
; Morris L
; Zhu W
; Zhao YD
; Suh KS
; Dooley WC
; Volk D
; Gorenstein DG
; Cristofanilli M
; Rui H
; Tanaka T
Mol Ther
2015[Jun]; 23
(6
): 1044-1054
PMID25815697
show ga
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.
|*Gene Expression Regulation, Neoplastic
[MESH]
|Animals
[MESH]
|Aptamers, Nucleotide/genetics/metabolism
[MESH]
|Breast Neoplasms/*genetics
[MESH]
|Cell Adhesion
[MESH]
|Cell Line, Tumor
[MESH]
|E-Selectin/genetics/metabolism
[MESH]
|Endothelial Cells/metabolism
[MESH]
|Female
[MESH]
|Genetic Therapy
[MESH]
|Humans
[MESH]
|MCF-7 Cells
[MESH]
|Mice
[MESH]
|Mice, Inbred BALB C
[MESH]
|Neoplasm Metastasis/genetics/*prevention & control
[MESH]
free
free
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