Encouragingly, Tetrocarcin-A downregulated JAM-A expression and caused cytotoxicity in primary breast cells and lung cancer stem cells, and inhibited the growth of xenografts in a semi-in vivo model involving invasion across the chicken egg chorioallantoic membrane.
In a murine xenograft model established with subcutaneous injection of JAM-A-overexpressing B-lymphoma cells, lenalidomide retarded tumor growth and prevented cell invasion to mesoendoderm-derived organs, consistent with the downregulation of JAM-A and NODAL expression.
On exploring whether TGF-β1 might be the upstream regulator of JAM-A expression, we found that knockdown of TGF-β receptors and canonical Smad signaling could upregulate JAM-A level and inhibit cell invasion in MDA-MB-231 cells.