Cells transfected with COL1A2, COL6A3, and THBS2 silencing sequences exhibited promoted apoptosis but inhibited proliferation, migration, and invasion.
Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2).
Importantly, knockdown of Thbs2 led to increased MMP3 expression and interruption of the ERα mediated invasion suppression, providing further evidence of an ERα-Thbs2-MMP3 axis in CAF.
Notably, the TSP2 epithelial staining score was significantly correlated to vascular invasion and biochemical recurrence in PCa tissue samples (P<0.05).
In vitro, addition of recombinant (rec) TSP-2 to mouse brain microvessel endothelial cells reduced MMP-2 levels and invasion through mechanisms that could be inhibited by a competitive inhibitor of ligand binding to LRP1 or by siLRP1.