title: Galectin-3 inhibits osteoblast differentiation through notch signaling.
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.
authors.affiliation: Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Kosei
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Dhong Hyo
authors.initials: DH
authors.lastname: Kho
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yanagawa
authors.affiliation: Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Harazono
authors.affiliation: Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Xiaoge
authors.initials: X
authors.lastname: Gao
authors.affiliation: Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Hogan
authors.affiliation: Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000235:genetics; D018613:Microscopy, Confocal; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D037502:Galectin 3; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; C497761:NOTCH1 protein, human; C493709:RUNX2 protein, human; D051881:Receptor, Notch1; D000469:Alkaline Phosphatase; D002118:Calcium