Cross talk between tumor-derived EVs and the matrix is strongly influenced by EV tetraspanins (CD151 and Tspan8), mainly due to their associations with integrins (ITGA3, ITGB4, and ITGAM) and proteases (MMP2, MMP9, MMP14, and CD13), which facilitate binding, motility, and matrix degradation. The gene discussed is TSPAN8; the disease is neoplasm.