The identification of a novel Paneth cell-associated antigen in a familial adenomatous polyposis mouse model

Wnt signaling is important for the differentiation of the Paneth cell lineage in the small intestine. However, abnormal Wnt signaling predisposes to intestinal tumorigenesis in the familial adenomatous polyposis (FAP) mouse model. Vaccination with dendritic cells fused with tumor cells from FAP mice, in which Wnt signaling is constitutively activated, induced humoral immunity and suppressed intestinal tumor development. We identified the novel antigen Apa1 (Adenomatous polyposis antigen 1) recognized by antibodies in vaccinated mouse serum. Apa1 was localized in the Paneth cell-like tumor cells showing cytoplasmic β-catenin accumulation and also in normal Paneth cells at the bottom of the crypts. Phospholipase A2 (Pla2g2a), known to act as an anti-bacterial agent and a major suppressor of intestinal tumors, was also expressed in the Paneth cells. These results suggest that Apa1 might be involved in anti-microbial defense and could influence tumor development in FAP mice via modulation of commensal microbiota.

Research highlights
► Abnormal Wnt signaling causes intestinal tumors
► Vaccination with intestinal tumor cells suppresses intestinal tumor development
► Vaccination induces humoral immunity against the novel antigen Apa1
► Abnormal Wnt signaling induces the aberrant differentiation of Paneth cells
► Paneth cell-like tumor cells showing abnormal Wnt signaling express Apa1