title: Blocking the adhesion cascade at the premetastatic niche for prevention of breast cancer metastasis.
abstract: 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.
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Shin-Ae
authors: SA
authors: Kang
authors: Department of Pharmaceutical Sciences, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors: Nafis
authors: N
authors: Hasan
authors: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: Aman P
authors: AP
authors: Mann
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Wei
authors: W
authors: Zheng
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Lichao
authors: L
authors: Zhao
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Lynsie
authors: L
authors: Morris
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Weizhu
authors: W
authors: Zhu
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: Yan D
authors: YD
authors: Zhao
authors: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersy, USA.
authors: K Stephen
authors: KS
authors: Suh
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors: William C
authors: WC
authors: Dooley
authors: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: David
authors: D
authors: Volk
authors: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors: David G
authors: DG
authors: Gorenstein
authors: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors: Massimo
authors: M
authors: Cristofanilli
authors: Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors: Hallgeir
authors: H
authors: Rui
authors: Department of Pathology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address: takemi-tanaka@ouhsc.edu.
authors: Takemi
authors: T
authors: Tanaka
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000235:genetics / Q000517:prevention & control*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics
chemical_list: D052157:Aptamers, Nucleotide; D019040:E-Selectin; D011960:Receptors, Estrogen