Among the processes involved in the breast tumor microenvironment, angiogenesis and inflammation play a central role, and the main factors of these processes are the vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2) and macrophages.
These data suggest that downregulation of RhoGDI could be a critical mechanism of breast tumor development, which may involve the hyperactivation of Rho GTPases and upregulation of COX-2 activity.
Furthermore, these results showed that LV-COX-2 combination with TAM is a potential drug candidate for treatment of breast tumors expressing high levels of VEGF.
Overall, these data identify a new p130Cas/Cyclooxygenase-2 axis as a crucial element in the control of breast tumor plasticity, opening new therapeutic strategies leading to inhibition of these pathways in aggressive breast carcinoma.
To elucidate the mechanisms by which exacerbated COX2 expression potentiates metastasis we genetically manipulated non-metastatic mammary tumor cells (TM40D) to over-express COX2 (TM40D-COX2).
By immunocytochemistry, Western blotting and flow cytometry analysis, oestrogen treatment of R2d cells was found to induce many important effects related to breast carcinogenesis, namely: (i) the emergence of a subpopulation of cells expressing CD44+/high/CD24-/low breast tumour stem cell markers; (ii) the induction of EMT (epithelial-to-mesenchymal transition); (iii) the acquisition of metastatic ability; and (iv) the expression of COX-2 (cyclo-oxygenase-2) through a CD44-mediated mechanism.
Cyclooxygenase-2 induces genomic instability, BCL2 expression, doxorubicin resistance, and altered cancer-initiating cell phenotype in MCF7 breast cancer cells.
Estrogen-dependent prognostic significance of cyclooxygenase-2 expression in early-stage invasive breast cancers treated with breast-conserving surgery and radiation.
15-Deoxy-Delta12,14-prostaglandin J2 induces COX-2 expression through Akt-driven AP-1 activation in human breast cancer cells: a potential role of ROS.
Cyclooxygenase-2 induces genomic instability, BCL2 expression, doxorubicin resistance, and altered cancer-initiating cell phenotype in MCF7 breast cancer cells.