Abstract
CEACAM20, a novel member of the CEACAM1 gene family with expression limited to the lumen of small intestine, testes, and prostate, is co-expressed with CEACAM1 in adult prostate tissue and down-regulated to the same extent as CEACAM1 in prostate cancer. Since prostate cancer often involves loss of epithelial lumen formation, we hypothesized that CEACAM20 and CEACAM1 play important roles in lumen formation of normal prostate epithelium. When prostate cells were grown on Matrigel as a source of extracellular matrix (ECM), they differentiated into acinar structures with single tubules and well-defined lumina closely resembling embryonic prostate organoids. Confocal microscopic analysis revealed restriction of CEACAM20 to acini and CEACAM1 to tubule structures, respectively. Inhibition of CEACAM1 with antibodies or soluble CEACAM1 or antisense oligonucleotides inhibited tubule formation by over 50% while the remaining tubules were stunted. Inhibition of CEACAM20 with antisense oligonucleotides completely inhibited tubule formation and stunted the growth of acini. We conclude that CEACAM20 and CEACAM1 not only mark the lumina of adult prostate tissue but also play a critical role in the vitro generation of prostate organoids.
Highlights
The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) gene family, a subgroup of the immunoglobulin superfamily, has 12 genes located on human chromosome 19
Since CEACAM20 exhibits an expression pattern in prostate similar to CEACAM1, we explored their function in the differentiation of the prostatic lumen in-Matrigel culture
It has been proposed that prostate cancer originates from luminal epithelial cells and that prostate intraepithelial neoplasia (PIN) is the precursor to carcinoma [36]
Summary
The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) gene family, a subgroup of the immunoglobulin superfamily, has 12 genes located on human chromosome 19. Their gene products mediate cell-cell adhesion among multiple cell types including epithelium, endothelium and lymphocytes, regulating diverse signal pathways including vasculogenesis [1], insulin clearance [2], cell growth [3] and apoptosis [4]. Its unusually long cytoplasmic domain has an immunoreceptor tyrosine-based activation motif (ITAM) conserved across the mouse, rat and human CEACAM20 genes. CEACAM20 transcripts are restricted to the reproductive system (prostate and Leydig cells) and the intestinal tract (colon, jejunum, ileum and cecum) [5]; its function has not been studied. Since prostate cancer is the second leading cause of cancer deaths in men (CDC report in 2007), we began functional studies of CEACAM20 in the prostate
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