Lactate in the TME as a possible signaling molecule in support of PEPT1 function.
Real-time PCR showing relative mRNA expression of MMP9 (A), MMP13 (B), MMP16 (C), and DPPIV (D) in control and lactate-treated SU.86.86 cells. Western blotting showing protein expression of MMP9, MMP13, MMP16, and DPPIV from total cell lysates of cultured Capan-1 and SU.86.86 vs. the tumor lysates from Capan-1 and SU.86.86 xenografted tumors. Beta-actin was used as a loading control (E). Real-time PCR showing relative PEPT1 mRNA expression in amino acid- and serum-starved Capan-1 and SU.86.86 cells restimulated with Phe (F and G) and Gly-Pro (H and I). PEPT1-mediated [3H]Gly-Sar uptake in amino acid- and serum-starved Capan-1 and SU.86.86 cells restimulated with Phe (J and N), Lys (K and O), Gly-Sar (L and P), and Gly-Phe (M and Q). Data are given as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.