In ER/PR/HER2(-) patients the OPN levels in breast tumors were significantly higher than in corresponding normal breast tissue samples, whereas in the single ER/PR/HER2(+) patient the OPN concentration in tumor samples was lower than in normal breast tissue sample.
Similarly, after intravenous administration of the osteopontin-750 probe, it accumulated preferentially in the subcutaneous breast tumor in nude mice (557 MSOT a.u. compared to untargeted organs such as kidney (53.7 MSOT a.u.) and liver (32.1 MSOT a.u.).
Elevated mRNA expression of SPP1 gene was revealed in breast tumors (2-7-fold) that correlated with SPP1 antigen immunoreactivity in autologous patients' sera.
ADAM9 silencing in MDA-MB-231 cells had no influence in expression of several genes related to the metastatic process such as ADAM10, ADAM12, ADAM17, cMYC, MMP9, VEGF-A, VEGF-C, osteopontin and collagen XVII.
Promotion of metastasis in response to miR-224 downregulation was associated with derepression of the stroma-associated RKIP target genes, CXCR4, MMP1, and OPN, which are involved in breast tumor metastasis to the bone.
Thus, we demonstrate for the first time a role for Merlin in impeding breast malignancy, identify a novel mechanism for the loss of Merlin protein in breast cancer, and have developed a discriminatory model using Merlin and OPN expression in breast tumor tissues.
Furthermore, the data showed that injection of carcinogenic compound, pristane (2, 6,10,14-tetramethylpen-tadecane) induces breast tumour progression leading to enhanced expression of OPN and other oncogenic molecules in mammary fat pad of nude- and wild-type mice but not in OPN-/- mice.
Thus, in addition to the widely reported roles of OPN in late stages of tumor progression, these results provide functional evidence that OPN contributes to breast tumor growth as well.
The mRNA level of OPN, a bone matrix protein associated with enhanced malignancy, increased in non-invasive, invasive, and liver and bone metastatic breast tumor tissue compared to normal breast tissue.