Constitutive expression of OPN in itself exerted partial invasiveness in vitro, but its expression itself was not sufficient to initiate tumor growth or metastasis formation in vivo.
In SW480 human colon cancer cells, we conclude that Sp1 mediated expression of the tumor metastasis protein, OPN, regulates in vitro functional correlates of tumor metastasis.
Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.
Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed.
Furthermore, the protein content of HCC principal tumor markers, CK19 and OPN, linked to the metastasis process was significantly reduced by METF stimulus.
Osteopontin (OPN) has been recognized as a significant cytokine in the processes of tumorigenicity, tumor progression and metastasis in many types of human cancer.
In this study, we show that while Wt.BRCA1 suppresses OPN-induced metastasis in a rat syngeneic system, Mut.BRCA1 enhances the development of metastasis through OPN, suggesting that OPN and BRCA1 work closely to regulate metastatic development in the rat.
In this study, RNA interference mediated by viral vectors-which could induce a long-lasting down-regulation in gene expression-was applied to analyze the role of OPN in metastasis of HCC.
Using a panel of genes identified by suppression subtractive hybridization of cDNAs from individual primary tumours and a metastasis, some cDNAs were found to exhibit a differential pattern of expression associated with the expression of S100A4 protein (including osteopontin, S100A9, claudin 2 and several Expressed Sequence Tags sequences).
The level of OPN protein expression was significantly associated with the patient's age (p = 0.04), tumor depth (p = 0.03), histological grade (p = 0.008), and hematogenous metastasis (p = 0.007).
Osteopontin (OPN) and autotaxin (ATX) are important chemokines involved in the survival, proliferation, migration, invasion, and metastasis of many cancer cells.
These results suggest that the presence of these transcription factors in human breast cancer is responsible in part for the overexpression of OPN that, in turn, is implicated in mammary neoplastic progression and metastasis.
Importantly, JNK inhibition or disruption of SPP1 or TNC expression sensitizes experimental mammary tumors and metastases to chemotherapy, thus providing insights to consider for future treatment strategies against metastatic breast cancer.