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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell adhesion molecules have been implicated in the selective colonization of cancer in distant organs. Breast cancer has a strong predilection for spreading to bone. Cadherin-11, which is one of the classical type-2 cadherin family members and mediates homophilic cell-cell adhesion, is constitutively expressed in stromal and osteoblastic cells in bone marrow. Elevated cadherin-11 expression is also found in aggressive human breast cancers. Here, we investigated the role of the interactions between breast cancer cells and bone marrow stromal/osteoblastic cells via cadherin-11 in the selective spread to bone. The bone-seeking clone of the MDA-MB-231 human breast cancer cells showed greater cadherin-11 expression than the parental and the brain-seeking clone. Cadherin-11 overexpression in MDA-MB-231 cells increased bone metastases with promoted bone resorption, while the natural variant form of cadherin-11 that is unable to establish cell-cell adhesion did not. Of note, introduction of cadherin-11 showed no effects on lung metastases. Fluorescence-activated cell sorter analysis using the fluorescent dye-labeled cancer cells showed that early colonization in bone marrow was increased by cadherin-11. Co-cultures with the MC3T3-E1 osteoblastic cells that constitutively expressed cadherin-11 caused an up-regulation of parathyroid hormone-related protein (PTH-rP) production in MDA-MB-231 cells overexpressing cadherin-11. The conditioned medium of the co-cultures increased osteoclastogenesis, which was blocked by a neutralizing antibody to PTH-rP. In conclusion, our results suggest that cadherin-11 promotes homing and migration to bone and osteoclastogenesis through mediating the homophilic interactions of breast cancer cells with marrow stromal/osteoblastic cells, thereby enhancing bone metastases.
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PMID:Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone. 1857 46

Bone is the most common site of metastases from prostate cancer. The mechanism by which prostate cancer cells metastasize to bone is not fully understood, but interactions between prostate cancer cells and bone cells are thought to initiate the colonization of metastatic cells at that site. Here, we show that cadherin-11 (also known as osteoblast-cadherin) was highly expressed in prostate cancer cell line derived from bone metastases and had strong homophilic binding to recombinant cadherin-11 in vitro. Down-regulation of cadherin-11 in bone metastasis-derived PC3 cells with cadherin-11-specific short hairpin RNA (PC3-shCad-11) significantly decreased the adhesion of those cells to cadherin-11 in vitro. In a mouse model of metastasis, intracardiac injection of PC3 cells led to metastasis of those cells to bone. However, the incidence of PC3 metastasis to bone in this model was reduced greatly when the expression of cadherin-11 by those cells was silenced. The clinical relevance of cadherin-11 in prostate cancer metastases was further studied by examining the expression of cadherin-11 in human prostate cancer specimens. Cadherin-11 was not expressed by normal prostate epithelial cells but was detected in prostate cancer, with its expression increasing from primary to metastatic disease in lymph nodes and especially bone. Cadherin-11 expression was not detected in metastatic lesions that occur in other organs. Collectively, these findings suggest that cadherin-11 is involved in the metastasis of prostate cancer cells to bone.
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PMID:Cadherin-11 promotes the metastasis of prostate cancer cells to bone. 1870 58

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.
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PMID:Cadherin-11 increases migration and invasion of prostate cancer cells and enhances their interaction with osteoblasts. 2048 40