The pancreatic tumor microenvironment comprises discreet domains and is regulated by crosstalk between PSCs and tissue macrophages

Abstract

s / Pancreatology 13 (2013) e1–e94 e73 Method: The CD18/HPAF and Capan-1 PC cells were treated with CI 1033. Western blot analysis was performed to investigate the effect of CI 1033 on the activation and expression of EGFR family members and their downstream signaling targets. Co-immunolocalisationwas also performed to analyze the correlation between the expression of EGFR family proteins and MUC4 on treatment with CI 1033. Real time PCR and immunoblotting was performed to analyze the effect of CI 1033 on MUC4 expression. Results: We observed decreased phosphorylation status of EGFR and HER-2 along with loss of total EGFR, HER2, HER3 and MUC4 levels on CI 1033 treatment. Similarly, the EGFR downstream signaling targets, such as pERK and pAKT and cyclin D1 and cyclin A also decreased on CI 1033 treatment. Additionally, treatment with CI 1033 led to significant induction of apoptosis, decreased proliferation and migration. Finally, mechanisms for MUC4 down regulation were confirmed by following expression of transcription factor Stat1. Conclusion: Our results demonstrate that CI 1033 is an attractive drug to inhibit the growth of human PC cells as it directly and indirectly affects EGFR family member downstream signaling and MUC4 downregulation, respectively.