Bone sialoprotein expression in primary human breast cancer is associated with bone metastases development

Abstract

Breast cancer metastasizes to bone more frequently than to any other organ, and over 80% of advanced breast cancer patients develop bone metastases. Our recent demonstration that human breast cancer cells express bone sialoprotein (BSP), a bone matrix protein, provides a possible clue for the selective affinity of breast cancer cells for bone. We tested the hypothesis that detection of BSP in primary human breast cancer could be a potential indicator of the ability of breast cancer cells to metastasize to bone. BSP expression was evaluated in the primary breast cancers of 39 patients using immunoperoxidase and two specific anti-BSP antibodies. None of these patients presented clinically or scintigraphically detectable bone metastases at the time of surgery. In the course of their disease, 22 patients developed clinically diagnosed bone metastases. Expression of BSP in breast cancer cells from patients who developed bone metastases was significantly higher (p = 0.008, according to the Mann-Whitney test) than in patients with no bone involvement. No association was found between BSP expression in the primary breast lesions and axillary lymph node metastases. BSP expression was significantly increased in infiltrating ductal carcinoma compared with infiltrating lobular carcinoma (p = 0.0023). No correlation was found between immunoreactivity to BSP antibodies and estrogen receptor (ER) status, progesterone receptor (PR) status, or age. Our data suggest that BSP could help to identity which women will develop bone metastases and provide new bases for the understanding of the molecular mechanism(s) responsible for breast cancer cells osteotropism.

A structural and functional model for human bone sialoprotein

“…have a total composition of (GalNAc) 16 (GlcNAc) 4 (Gal) 15 (Glc) 6 (NeuAc) 16 Figure 1, and the predictions of the NetOGlyc server [25]. We then selected the eight most likely sites on this basis.…”

“…Thus, one dimensional 1 H NMR of recombinant BSP revealed that the protein is highly flexible along its entire length and exists as an ensemble of A c c e p t e d M a n u s c r i p t 4 completely unstructured conformations in solution [4]. Similarly, two dimensional HSQC NMR of an 15 N labelled recombinant BSP fragment taken from the last 59 amino acids of the protein C-terminus indicated a rapidly flexing random coil structure [5]. Secondary structure prediction programs such as PsiPred [6] also suggest that the unmodified BSP would exist as an essentially unstructured random coil.…”

“…Along with the related SIBLING (small integrin binding ligand, N-linked glycoprotein) protein osteopontin, BSP is expressed in malignant tissues, and indeed elevated serum levels of these proteins can be used to detect several types of cancer [13]. Expression of BSP is strongly associated with bone metastases in lung [14] and bone [15] tissues.…”

Influence of pneumoperitoneum on tumor implantation in parietal incision: a comparative study of trocar incision and laparotomy in rats

“…The literature indicates 1x10 7 and 2x10 5 viable tumor cells as adequate for intraperitoneal inoculation in Wistar rats, as this amount produces ascites and death within approximately seven days 58,86,87,92 . The fact of tumor dissemination observed in all animals of the experiment can be explained by the formation of new blood vessels [95][96][97] , as it occurs in normal healing process of surgical wounds, and by the loss of cohesion between tumor tissue cells 98 and increased cell motility 99 , resulting from tumor manipulation in rats of group A of laparotomy, and by the flow of gas in pneumoperitoneum in group B.…”

Breast Cancer Metastases to Bone: Role of the Microenvironment

“…However, breast cancer cells have been shown to express both BSP and OPN, and to upregulate BSP expression in pre-osteoblasts through BMP signalling; and OPN was found localized between cancer cells and bone cells at sites of metastasis (116,117). Moreover, the expression of BSP has been found to correlate with bone metastasis development (118), and OPN expression and serum concentrations have been shown to be poor prognosis markers in breast cancer patients (119,120). As osteopontin is also a mediator of the hematopoietic stem cell niche, directing migration and acting as an adhesion molecule to HSC via 1 integrin (121), it represents a potentially valuable therapeutic target against bone metastases.…”