Since S100A8 and S100A9 are calcium binding proteins, the complexity of their effects on tumor biology may depend not only on TLR4 and/or RAGE ligation, but also on alterations in intracellular calcium fluxes and/or concentrations, demonstrated to occur in pancreatic β-cells exposed to the 14 N-terminal aminoacid peptide of S100A8 (NT-S100A8), which we isolated from PDAC tissues of patients with PDAC-associated diabetes mellitus [34]. This evidence concerns the gene S100A8 and neoplasm.