SPP1 and neoplasm: Our results demonstrate that OPN stimulates CNSL tumor cell proliferation, tumor growth, brain tissue invasiveness and intracerebral dissemination through a novel mechanism whereby OPN activates NF-κB activity via a novel dual mechanism in which intracellular OPN (iOPN) transcriptionally downregulates endogenous inhibitors of NF-ĸB, and secretory OPN (sOPN) directly activates NF-κB via an autocrine loop.