Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer.

Background: Endo180 (CD280; MRC2; uPARAP)-dependent collagen remodelling is dysregulated in primary tumours and bone metastasis. Here, we confirm the release and diagnostic accuracy of soluble Endo180 for diagnosing metastasis in breast cancer (BCa).

Methods: Endo180 was quantified in BCa cell conditioned medium and plasma from BCa patients stratified according to disease status and bisphosphonate treatment (n=88).

TGFβ1-Endo180-dependent collagen deposition is dysregulated at the tumour-stromal interface in bone metastasis.

Cellular niches in adult tissue can harbour dysregulated microenvironments that become the driving force behind disease progression. The major environmental change when metastatic cells arrive in the bone is the destruction of mineralized type I collagen matrix. Once metastatic niches establish in bone, the invading tumour cells initiate a vicious cycle of osteolytic lesion formation via the dysregulation of paracrine signals and uncoupling of normal bone resorption and production.

Endo180 expression with cofunctional partners MT1-MMP and uPAR-uPA is correlated with prostate cancer progression.

Endo180 (CD280; MRC2; uPARAP) regulates collagen remodelling and chemotactic cell migration through cooperation with membrane type-1 matrix metalloproteinase (MT1-MMP), urokinase-type plasminogen activator receptor (uPAR) and urokinase-type plasminogen activator (uPA). One hundred and sixty nine prostate tissue sections clinically graded as benign prostatic hyperplasia (BPH) (n=29) or prostate cancer (PCA) with Gleason scores indicating low (< or =7(3+4); n=26), intermediate (7(4+3)-8; n=96) or high (9-10; n=19) clinical risk were immunofluorescently stained for Endo180, pan-cytokeratin (pCk), vimentin, MT1-MMP and uPAR-uPA. Quantification of % Endo180(+)/pCk(-) and Endo180(+)/pCk(+) cells in entire tissue cores revealed stromal (p=0.

Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction.

Introduction: Osteocyte apoptosis co-localizes with sites of osteoclastic bone resorption in vivo, but to date, no causal molecular or signaling link has been identified between these two processes.

Materials And Methods: Osteocyte apoptotic bodies (OABs) derived from the MLO-Y4 osteocyte-like cell line and primary murine osteocytes and apoptotic bodies (ABs) derived from primary murine osteoblasts were introduced onto the right parietal bone of murine calvariae, and osteoclastic bone resorption was examined 5 days after treatment. In addition, the ability of primary murine and cell line-derived OABs to support osteoclastogenesis was examined in vitro in co-culture with murine bone marrow hematopoietic progenitors in the absence of RANKL or macrophage-colony stimulating factor.

Mannose receptor regulation of macrophage cell migration.

The migration of macrophages through peripheral tissues is an essential step in the host response to infection, inflammation, and ischemia as well as in tumor progression and tissue repair. The mannose receptor (MR; CD206, previously known as the macrophage MR) is a 175-kDa type I transmembrane glycoprotein and is a member of a family of four recycling endocytic receptors, which share a common extracellular domain structure but distinct ligand-binding properties and cell type expression patterns. MR has been shown to bind and internalize carbohydrate and collagen ligands and more recently, to have a role in myoblast motility and muscle growth.

The biology of osteocytes.

Osteocytes, the most abundant cell type in bone, remain the least characterized. Several theories have been proposed regarding their function, including osteolysis, sensing the strains produced in response to mechanical loading of bones, and producing signals that affect the function of osteoblasts and osteoclasts and hence, bone turnover. This review also discusses the role of osteocyte apoptosis in targeted bone remodeling and proposes that the occurrence of osteocyte apoptosis is consistent with the description of apoptosis as an essential homeostatic mechanism for the healthy maintenance of tissues.

The influence of mechanical stimulation on osteocyte apoptosis and bone viability in human trabecular bone.

It has been shown previously using in vivo and ex vivo animal models, that cyclical mechanical stimulation is capable of maintaining osteocyte viability through the control of apoptotic cell death. Here we have studied the effect of mechanical stimulation on osteocyte viability in human trabecular bone maintained in a 3-D bioreactor system. Bone samples, maintained in the bioreactor system for periods of 3, 7 and 27 days, were subjected to either cyclical mechanical stimulation which engendered a maximum of 3,000 microstrain in a waveform corresponding to physiological jumping exercise for 5 minutes daily or control unloading.

The antioxidant effect of estrogen and Selective Estrogen Receptor Modulators in the inhibition of osteocyte apoptosis in vitro.

Withdrawal of estrogen represents the primary factor determining post menopausal bone loss and has been associated with negative indicators of bone quality including the apoptotic death of osteocytes in vivo. While hormone replacement therapy in the form of Estrogen or Selective Estrogen Receptor Modulators (SERMs) demonstrates clear estrogen receptor (ER)-mediated benefits to bone mass, less is known regarding the mechanism of action of these compounds in the maintenance of bone cell populations. We have investigated the potential antioxidant effects of estrogen, estrogen derivatives and the SERMs Raloxifene and LY117018 in the prevention of oxidative stress induced apoptosis in the osteocyte like cell line MLO-Y4.

Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis.

Prolonged use of glucocorticoids is associated with decreased bone formation, increased resorption and osteonecrosis, through direct and indirect effects on the activity and viability of bone effector cells, osteoblasts and osteoclasts, and osteocytes. This study has investigated molecular pathways implicated in Dexamethasone-induced apoptosis of osteocytes, using a cell line and primary chicken cells. MLO-Y4 osteocytes were pre-treated with several bisphosphonates representing a range of anti-resorptive activities and conformation/structure relationships, and were subsequently challenged with Dexamethasone.