Taken together, host and tumor Tspan8 and CD151 contribute to tumor progression, with only a partial overlap of Tspan8- and CD151-deficits, apparent by the stronger defects of dbko-MCA in dissemination, more strongly impaired angiogenesis of CD151ko MCA and more pronounced deficits in Tspan8ko MCA in distant organ settlement. Here, TSPAN8 is linked to neoplasm.