CC chemokine receptor 9 enhances proliferation in pancreatic intraepithelial neoplasia and pancreatic cancer cells

Abstract

Introduction: Chemokine receptors may regulate the progression and metastasis of invasive malignancies. There are little data, however, regarding their role in premalignant lesions. Our objective was to determine the role of CC chemokine receptor 9 (CCR9) in pancreatic intraepithelial neoplasia (PanIN).

Methods: Human and murine formalin-fixed paraffin-embedded (FFPE) PanIN specimens were assessed for CCR9 expression. The established murine PanIN, invasive pancreatic cancer (5143PDA) and liver metastasis (5143LM) cell lines, and human pancreatic cancer cell line (PANC-1) were obtained to verify CCR9 expression and function.

Results: Immunohistochemistry of FFPE specimens demonstrated CCR9 expression in both murine and human PanIN lesions. CCR9 expression in murine and human cell lines was verified by Western blot assay, immunofluorescence, and flow cytometry. CCR9 function was demonstrated by in vitro exposure to CCL25, the selective CCR9 ligand, which resulted in significantly increased cell proliferation in PanIN and pancreatic cancer cell lines.

Conclusions: This is the first report of chemokine receptor CCR9 expression in murine and human PanIN tissues. Our results demonstrate enhanced PanIN and pancreatic cancer cell proliferation with activation of CCR9 by its selective ligand CCL25. CCR9 may prove to be a novel therapeutic target for PanIN and its progression to invasive cancer.