TY - JOUR
T1 - Cadherin-11 increases migration and invasion of prostate cancer cells and enhances their interaction with osteoblasts
AU - Huang, Chih Fen
AU - Lira, Cristina
AU - Chu, Khoi
AU - Bilen, Mehmet Asim
AU - Lee, Yu Chen
AU - Ye, Xiangcang
AU - Kim, Soo Mi
AU - Ortiz, Angelica
AU - Wu, Fe Lin Lin
AU - Logothetis, Christopher J.
AU - Yu-Lee, Li Yuan
AU - Lin, Sue Hwa
PY - 2010/6/1
Y1 - 2010/6/1
N2 - 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 β-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-ΔJMD-expressing or cad11-ΔCBS-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.
AB - 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 β-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-ΔJMD-expressing or cad11-ΔCBS-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.
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U2 - 10.1158/0008-5472.CAN-09-3016
DO - 10.1158/0008-5472.CAN-09-3016
M3 - Article
C2 - 20484040
AN - SCOPUS:77953153372
SN - 0008-5472
VL - 70
SP - 4580
EP - 4589
JO - Cancer Research
JF - Cancer Research
IS - 11
ER -