title: Suppression of prostate cancer cell rolling and adhesion to endothelium by 1α,25-dihydroxyvitamin D3.
abstract: Adhesion of circulating prostate cancer (PCa) cells to the microvascular endothelium is a critical step during cancer metastasis. To study PCa cell rolling and adhesion behavior, we developed a dynamic flow-based microtube system to mimic the microvascular environment. We found that PCa cell rolling capacity is mediated by E-selectin and can be enhanced by stromal cell-derived factor-1 under different wall shear stresses. Using this device, we tested if the chemopreventive agent, vitamin D, could interfere with PCa cell adhesion. We found that 1α,25-dihydroxyvitamin D(3) (1,25-VD), the bioactive form of vitamin D, reduced PCa cell rolling numbers and increased rolling velocities resulting in a significant decreased number of PCa cells adhering to the microtube. The inhibitory effects of 1,25-VD on PCa cell heterotypic adhesion were further confirmed using microvascular endothelial cells in a static condition. Furthermore, we demonstrated that 1,25-VD can increase E-cadherin expression in PCa cells and promote the homotypic cell-cell aggregation, which can then hinder PCa cell adhesion to the endothelium. Blocking E-cadherin with a neutralizing antibody can reverse 1,25-VD-mediated suppression of PCa cell adhesion to the endothelium. Taken together, our data revealed that 1,25-VD promoted PCa cell aggregation by increasing E-cadherin expression, thus interfering with circulating PCa cell adhesion to microvascular endothelial cells and potentially reducing their metastatic potential.
authors.affiliation: Department of Urology and Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Jong-Wei
authors.initials: JW
authors.lastname: Hsu
authors.forename: Sayeda
authors.initials: S
authors.lastname: Yasmin-Karim
authors.forename: Michael R
authors.initials: MR
authors.lastname: King
authors.forename: Joel C
authors.initials: JC
authors.lastname: Wojciechowski
authors.forename: Deanne
authors.initials: D
authors.lastname: Mickelsen
authors.forename: Martha L
authors.initials: ML
authors.lastname: Blair
authors.forename: Huei-Ju
authors.initials: HJ
authors.lastname: Ting
authors.forename: Wen-Lung
authors.initials: WL
authors.lastname: Ma
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Lee
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000187:drug effects* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012212:Rheology / Q000187:drug effects; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D054377:Chemokine CXCL12; D019040:E-Selectin; D012333:RNA, Messenger; C118756:dihydroxy-vitamin D3; D014807:Vitamin D