Abstract
Bone sialoprotein (BSP) has been implicated in a variety of physiological and pathophysiological events, including tumor cell invasion, bone homing, adhesion, and matrix degradation. To explore the potential involvement of BSP in human breast cancer cell invasion and metastasis, we used retrovirus-mediated RNAi to deplete BSP levels in the human bone-seeking breast cancer cell line MDA-MB-231BO (231BO) and established the 231BO-BSP27 and 231BO-BSP81 cell clones. Cell proliferation, colony formation, wound healing, and the ability to invade into matrigel of these BSP-depleted clones were all decreased. Both 231BO-BSP27 cells and 231BO-BSP81 cells showed a significant (15.4% and 28.6% respectively) reduction of bone metastatic potential following intracardiac injection as determined by X-ray detection and by hematoxylin and eosin staining. Moreover, the expression of integrins αvβ3 and β3 was decreased in the BSP-silenced cells whereas ectopic BSP expression increased the integrins αvβ3 and β3 levels. These results together suggest that BSP silencing decreased the integrin αvβ3 and β3 levels, in turn inhibiting cell migration and invasion and decreasing the ability of the cells to metastasize to bone.
Highlights
Breast cancer is a common malignancy among women
Bone sialoprotein (BSP)-silenced Cell Clones were Established As detected by western blot, the BSP27 or the BSP81 shRNA
Colony formation showed a 48.8% or a 53.7% decrease in 231BO-BSP27 or 231BO-BSP81 cells compared to 231BOScrambled cells (p,0.05) (Fig. 2B)
Summary
Breast cancer is a common malignancy among women. While locally contained in situ tumors can be surgically removed, the major threat arises from tumor cells that invade adjacent tissues or metastasize to distant sites [1]. Bone is a common site of metastasis; 64% of patients who die from breast cancer have bone metastases [2]. Bone sialoprotein (BSP) is a highly phosphorylated and glycosylated secreted protein in the bone matrix, belonging to the class of molecules known as small integrin binding ligand Nlinked glycoproteins, or SIBLINGs. Its expression is not restricted to bone, and, it has been described as a common extracellular protein secreted by human breast cancer cells [3,4,5]. BSP contains an integrinbinding RGD (Arg-Gly-Asp) sequence that may mediate protein binding to the cell surface [8] and may promote interactions between cells and the bone matrix through avb and avb integrin receptors [9]. While over-expression of BSP promotes bone metastasis of human breast cancer cells in mouse models [5,11], a decrease in BSP levels in breast cancer cells, using either antisense BSP cDNA or anti-BSP antibody, inhibits bone metastasis in vitro and in vivo [12,13,14,15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
