Differential CD74 (major histocompatibility complex Class II invariant chain) expression in mouse and human intestinal adenomas

CD74 (major histocompatibility complex (MHC) Class II invariant chain) has recently been identified as the cell-surface receptor for the pro-tumorigenic cytokine macrophage migration inhibitory factor (MIF). Therefore, we investigated CD74 gene expression in intestinal adenomas in ApcMin/+ mice and humans. CD74 mRNA (p31 and p41 splice variants) and immunoreactive CD74 protein levels were significantly lower in small intestinal and colonic ApcMin/+ mouse adenomas compared with histologically normal mucosa. These findings were mirrored by a reduction in MHC Class II expression and Class II trans-activator type IV transcripts. Conversely, CD74 protein levels were actually increased in dysplastic epithelial cells in 47/55 (85%) human colorectal adenomas, with CD74 and MIF protein levels together predicting increasing dysplasia in individual adenomas (P = 0.003). Down-regulation of CD74 during ApcMin/+ mouse intestinal tumorigenesis does not model increased CD74 expression at the early, benign stages of human colorectal carcinogenesis. Epithelial cell CD74 represents a valid target for anti-CRC therapy.