Figure 12.

Compared to empty vector, WT-ASPH significantly enhanced metastatic capability of MDA-MB-231 cells, which was efficiently reversed by the SMI in experimental pulmonary metastatic (tail vein injection) murine model. (A) Experimental design and (B) Therapeutic protocol for tail vein injection model (n = 5/group). (C) Using fluorescent imaging system to detect potential pulmonary metastasis in mice from different groups of tail vein injection model. (D) The number of macro-metastases in the lungs derived from mice in tail vein injection model. *P < 0.05; **P < 0.01. (E) Gross appearance of the lungs derived from representative mice in tail vein injection model. Metastatic lesions were highlighted with yellow arrows. (F) Gross appearance and histopathologic characteristics of (Upper) hepatic and (Bottom) pulmonary metastatic lesions of a representative mouse in ASPH+DMSO group of tail vein injection model. Noted the metastatic lesions also maintain high expression of ASPH. This animal was euthanized at 7^th weeks. (G) Gross appearance of bone (spine) metastasis derived from a representative mouse in tail vein injection model. The mouse was tail vein injected with ASPH overexpressing MDA-MB-231 cells and treated with DMSO. (H) Histologic characteristics of bone and lung lesions in this specific mouse in (P). (I, J) Expression profiling of key components in SRC signaling pathway (p-SRC Y416, SRC regulator ADAM12 and downstream MMPs) was substantially downregulated by SMI.