Article

One NOTCH Further: Jagged 1 in Bone Metastasis

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Cancer cell (Impact Factor: 23.89). 02/2011; 19(2):159-61. DOI: 10.1016/j.ccr.2011.01.043
Source: PubMed

ABSTRACT The outgrowth of metastatic cells to bone depends on the interaction between multiple intrinsic and host factors. In this issue of Cancer Cell, Sethi and colleagues report Notch signaling in bone cells as responsible for promoting this outgrowth and provide evidence for a beneficial treatment effect of NOTCH inhibitors.

Download full-text

Full-text

Available from: Jianning Tao, Aug 25, 2015
0 Followers
 · 
109 Views
 · 
0 Downloads
  • Source
    • "On the basis of the fact that the circulating galectin-3 induces angiogenesis affecting tumor cell growth in the microenvironment [15] [16] [17], we examined its role in the bone. Tumor-derived jagged-1, a membrane-associated protein inducing Notch signaling expression, was reported to be associated with galectin-3 [18] and causes bone remodeling through cell-to-cell interaction between cancer cells and osteoclasts or osteoblasts [19]. A recent study reported that jagged-1 overexpressed in bone metastatic lesions of patients with breast cancer, implicating the potential role of Notch signaling in bone metastasis [20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with bone cancer metastasis suffer from unbearable pain and bone fractures due to bone remodeling. This is caused by tumor cells that disturb the bone microenvironment. Here, we have investigated the role of tumor-secreted sugar-binding protein, i.e., galectin-3, on osteoblast differentiation and report that it downregulates the expression of osteoblast differentiation markers, e.g., RUNX2, SP7, ALPL, COL1A1, IBSP, and BGLAP, of treated human fetal osteoblast (hFOB) cells. Co-culturing of hFOB cells with human breast cancer BT-549 and prostate cancer LNCaP cells harboring galectin-3 has resulted in inhibition of osteoblast differentiation by the secreted galectin-3 into culture medium. The inhibitory effect of galectin-3 was found to be through its binding to Notch1 in a sugar-dependent manner that has led to accelerated Notch1 cleavage and activation of Notch signaling. Taken together, our findings show that soluble galectin-3 in the bone microenvironment niche regulates bone remodeling through Notch signaling, suggesting a novel bone metastasis therapeutic target.
    Neoplasia (New York, N.Y.) 11/2014; 16(11). DOI:10.1016/j.neo.2014.09.005 · 5.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast cancer cells incorporate the simple sugar alpha-L-fucose (fucose) into glycoproteins and glycolipids which, in turn, are expressed as part of the malignant phenotype. We have noted that fucose is not simply a bystander molecule, but, in fact, contributes to many of the fundamental oncologic properties of breast cancer cells. Here, we summarize the evidence from us and others that fucose is necessary for key functions of neoplastic progression including hematogenous metastasis, tumor invasion through extracellular matrices including basement membranes and up-regulation of the Notch signaling system, with implications for epithelial-to-mesenchymal transition and activation of breast cancer stem cells. Additionally, certain breast cancer biomarkers are fucose-rich while a well-known marker of breast cancer progression, soluble E-selectin, is a known counter-receptor of fucosylated selectin ligands. We provide illustrative examples and supportive evidence drawn from work with human breast cancer cell lines in vitro as well as clinical studies with human pathologic material. And finally, we discuss evidence that fucose (or its absence) is central to the mechanisms of action of several experimental targeted therapies which may prove useful in breast cancer treatment. We propose that alpha-L-fucose is essential in order to construct first, the malignant and then the metastatic phenotype of many human breast cancers. This knowledge may inform the search for novel treatment approaches in breast cancer.
    American Journal of Translational Research 08/2011; 3(4):292-322. · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To summarize promising areas of investigation in osteoporosis and to stimulate further research in this area, as discussed in a recent international conference. Over the recent years, there has been an improvement in the knowledge of molecular pathways involved in bone formation and resorption with the development of new drugs to treat osteoporosis. Intact parathyroid hormone, teriparatide, and anti-sclerostin monoclonal antibody are anabolic drugs, whereas denosumab and odanacatib are anti-resorptive drugs with more reversible effects as compared to bisphosphonates. Anabolic and anti-resorptive agents have different effects on bone, and research in this area includes the efficacy of combination and sequential therapies with them. New insights in the molecular pathways of bone remodeling have clarified the mechanisms responsible for skeletal fragility in several forms of secondary osteoporosis, such as that occurring in type 2 diabetes, following drug exposure and systemic inflammatory diseases. Future research is needed to address the efficacy of anti-osteoporotic drugs in these more recently recognized conditions of skeletal fragility. Osteoporosis continues to be an important field of biomedical research.
    Endocrine 12/2011; 41(1):58-69. DOI:10.1007/s12020-011-9570-2 · 3.53 Impact Factor
Show more