City of Hope Irell & Manella Graduate School of Biological Sciences, Duarte, California, USA.
PLoS One. 2013;8(1):e53359. doi: 10.1371/journal.pone.0053359. Epub 2013 Jan 24.
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.
CEACAM20 是 CEACAM1 基因家族的一个新成员，其表达仅限于小肠、睾丸和前列腺的管腔中，在成人前列腺组织中与 CEACAM1 共同表达，并在前列腺癌中与 CEACAM1 下调到相同程度。由于前列腺癌通常涉及上皮管腔形成的丧失，我们假设 CEACAM20 和 CEACAM1 在正常前列腺上皮的管腔形成中发挥重要作用。当前列腺细胞在 Matrigel 上生长作为细胞外基质 (ECM) 的来源时，它们分化成具有单个小管和清晰定义的管腔的腺泡结构，类似于胚胎前列腺类器官。共聚焦显微镜分析显示 CEACAM20 局限于腺泡，CEACAM1 局限于管状结构。用抗体或可溶性 CEACAM1 或反义寡核苷酸抑制 CEACAM1 可抑制管状结构的形成超过 50%，而剩余的管状结构则发育不良。用反义寡核苷酸抑制 CEACAM20 可完全抑制管状结构的形成并阻碍腺泡的生长。我们得出结论，CEACAM20 和 CEACAM1 不仅标记成人前列腺组织的管腔，而且在体外生成前列腺类器官中发挥关键作用。
