Protein expression of the truncated neurokinin‐1 receptor (NK‐1R) is increased in dysplastic and malignant epithelial cells from patients with colitis associated colon cancer (CAC)

Patients with chronic ulcerative colitis have a high risk of developing CAC. The mechanisms by which chronic inflammation participates in the transition to CAC are unclear. The NK‐1R, which binds substance P, is expressed in two forms: full‐length (FL‐NK‐1R) and truncated (TR‐NK‐1R). Our previous work showed an increase in TR‐NK‐1R mRNA between high grade dysplasia (HGD) and CAC; however, the expression of the TR‐NK‐1R protein levels has not been studied in patients with CAC. Eight colectomy specimens were obtained from CAC patients. From each colon, quiescent colitis (QC), HGD or CAC sections were identified. NK‐1R levels were quantified using immunofluorescence with two antibodies: one targeting a C‐terminal epitope that binds only FL‐NK‐1R and one targeting an internal epitope that binds both. Mean fluorescent intensities of five representative epithelial fields were quantified using image analysis (ImageJ, NIH). We show an increase in cell surface expression of total NK‐1R among the QC, HGD and CAC groups (p<0.05), but no change in FL‐NK‐1R among groups indicating an increase in TR‐NK‐1R between the QC, HGD and CAC groups ( See Table). These data suggest that the TR‐NK‐1R may play a role in inflammation‐induced colon cancer and represents a potential target for therapy. Support: Robert and Dana Smith Family Foundation; Smithwick Endowment, Department of Surgery, Boston University School of Medicine.