Cadherin-11 increases migration and invasion of prostate cancer cells and enhances their interaction with osteoblasts.
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.
Huang
Chih-Fen
CF
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.
Lira
Cristina
C
Chu
Khoi
K
Bilen
Mehmet Asim
MA
Lee
Yu-Chen
YC
Ye
Xiangcang
X
Kim
Soo Mi
SM
Ortiz
Angelica
A
Wu
Fe-Lin Lin
FL
Logothetis
Christopher J
CJ
Yu-Lee
Li-Yuan
LY
Lin
Sue-Hwa
SH
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
D015820:Cadherins; C086960:osteoblast cadherin