ADAM12 expression in breast tumor cells correlated with a significant upregulation of proangiogenic factors such as VEGF and MMP-9 and downregulation of antiangiogenic factors such as Thrombospondin-1 (THBS1/TSP1) and Tissue Inhibitor of Metalloproteinases-2 (TIMP-2).
Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis.
Preliminary data from our laboratory using neutralizing antibodies suggested that the upregulation in breast tumor cell invasion seen in response to TSP-1 involved the urokinase plasminogen activator receptor (uPAR).
Although the conjugated peptides were inactive in vivo, an unconjugated retro-inverso analog of the native TSP peptide inhibited breast tumor growth in a mouse xenograft model.