In summary, we have characterized the expression and function of GPNMB/OA in three NSCLC cell lines (SK-MES-1, A549 and calu-6 cells) with the following key observations: (i) the shedding of GPNMB/OA ECD protein by NSCLC cells is directly correlated with GPNMB/OA mRNA levels; (ii) GPNMB/OA ECD protein plays an influential role in promoting cell migration, invasion and adhesion to a model ECM; and (iii) shedding of GPNMB/OA ECD protein to tumor tissues may contribute directly to the progression of lung cancer based on studies in athymic (nu/nu) mice. Here, GPNMB is linked to lung cancer.