SPP1 and neoplasm: Both full-length SPP1 and its proteolytically cleaved fragments play complementary yet distinct roles in tumor progression: cleaved SPP1 fragments, by exposing cryptic integrin-binding motifs, exhibit enhanced pro-invasive and immunosuppressive activities through promoting cell adhesion, migration, and remodeling of the tumor microenvironment, whereas the full-length protein and its splice variants sustain tumor cell survival and stemness via CD44/integrin-mediated signaling.