Tumor cells are the source of osteopontin and bone sialoprotein expressionin human breast cancer

Bone sialoprotein (BSP) and osteopontin (OPN) are secreted glycoproteins wi th a conserved Arg-Gly-Asp (RGD) integrin-binding motif and are expressed p redominantly in bone. The RGD tripeptide is commonly present in extracellul ar attachment proteins and has been shown to mediate the attachment of oste osarcoma cells and osteoclasts. To determine the origin and incidence of BS P and OPN mRNA expression in primary tumor, a cohort of archival, primary i nvasive breast carcinoma specimens was analyzed. BSP transcripts were detec ted in 65% and OPN transcripts in 77% of breast cancers examined. In genera l, BSP and OPN transcripts were detected in both invasive and in situ carci noma components. The transcripts were not detected in surrounding stromal c ells or in peritumoral macrophages. Despite its abundance in carcinomas, BS P expression was not detected in a panel of 11 human breast cancer cell lin es (MCF-7, T47D, SK-Br-3, MDA-MB-453, MDA-MB-231, MDA-MB-436, BT549, MCF-7( ADR), Hs578T, MDA-MB-435, and LCC15-MB) and OPN expression was detected onl y in two of these (MDA-MB-435 and LCC15-MB). To examine the possibility tha t expression of these genes was down-regulated in cell culture, several cel l lines were grown as nude mouse xenografts in vivo; however, these tumors also failed to express BSP. OPN expression was identified in all cell lines grown as nude mouse xenografts. Our data suggest that in human primary bre ast tumors, the origin of BSP and OPN mRNA is predominantly the breast canc er cells and that expression of these transcripts is influenced by the tumo r environment.