title: Cadherin-11 increases migration and invasion of prostate cancer cells and enhances their interaction with osteoblasts.
abstract: Cell adhesion molecules have been implicated in the colonization of cancer cells to distant organs. Prostate cancer (PCa) has a propensity to metastasize to bone, and cadherin-11, which is an osteoblast cadherin aberrantly expressed in PCa cells derived from bone metastases, has been shown to play a role in the metastasis of PCa cells to bone. However, the mechanism by which cadherin-11 is involved in this process is not known. Here, we show that expression of cadherin-11 in cadherin-11-negative C4-2B4 cells increases their spreading and intercalation into an osteoblast layer and also stimulates C4-2B4 cell migration and invasiveness. The downregulation of cadherin-11 in cadherin-11-expressing metastatic PC3 cells decreases cell motility and invasiveness. Further, both the juxtamembrane (JMD) and beta-catenin binding domains (CBS) in the cytoplasmic tail of cadherin-11 are required for cell migration and invasion, but not spreading. Gene array analyses showed that several invasion-related genes, including MMP-7 and MMP-15, are upregulated in cadherin-11-expressing, but not in cad11-DeltaJMD-expressing or cad11-DeltaCBS-expressing, C4-2B4 cells. These observations suggest that cadherin-11 not only provides a physical link between PCa cells and osteoblasts but also increases PCa cell motility and invasiveness that may facilitate the metastatic colonization of PCa cells in bone.
authors.affiliation: Departments of Molecular Pathology, Genitourinary Medical Oncology, and System Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Chih-Fen
authors.initials: CF
authors.lastname: Huang
authors.forename: Cristina
authors.initials: C
authors.lastname: Lira
authors.forename: Khoi
authors.initials: K
authors.lastname: Chu
authors.forename: Mehmet Asim
authors.initials: MA
authors.lastname: Bilen
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lee
authors.forename: Xiangcang
authors.initials: X
authors.lastname: Ye
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Angelica
authors.initials: A
authors.lastname: Ortiz
authors.forename: Fe-Lin Lin
authors.initials: FL
authors.lastname: Wu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Yu-Lee
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
mesh_terms: D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017434:Protein Structure, Tertiary; D014162:Transfection
chemical_list: D015820:Cadherins; C086960:osteoblast cadherin