Sema4D is a transmembrane protein (capable of short range cell-cell signaling); however, upon shedding by MT1-MMP it is converted into a soluble form, which may bind to its main receptor PlexinB1 expressed on the surface of multiple cell types in the tumor microenvironment, including cancer cells, endothelial cells and immune cells. This evidence concerns the gene PLXNB1 and neoplasm.