In the present paper, we explored the functional behavior of two NSCLC cell lines, A549 and Calu-1, following treatment with a combination of soluble factors, i.e., IL-6, IL-8, TGF-β and CXCL-16, known to be secreted by CAFs I [9,10,11,38,39,80,81] to recreate, at least in part, the stimuli exerted in vivo on tumor cells by a microenvironment permissive for cancer growth and progression. This evidence concerns the gene CXCL16 and neoplasm.