Colon Crypts of Subjects With Familial Adenomatous Polyposis Show an Increased Number of LGR5+ Ectopic Stem Cells.
Colon Crypts of Subjects With Familial Adenomatous Polyposis Show an Increased Number of LGR5+ Ectopic Stem Cells.
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DOI：
10.14309/ctg.0000000000000353
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发表时间：
2021-05-17
影响因子：
3.6
通讯作者：
Casey G
中科院分区：
文献类型：
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作者：
Jennelle LT;Dampier CH;Tring S;Powell S;Casey G
家族性腺瘤性息肉病(FAP)是一种遗传性结直肠癌(CRC)综合征，其特征是由于WNT信号通路(APC)基因的APC调节基因的遗传(或从头)突变而加速腺瘤的发展。FAP受试者息肉发展加速的机制尚未明确。鉴于LGR5+干细胞驱动隐窝细胞增殖，我们假设FAP隐窝将显示异常的亮氨酸富含重复序列的G蛋白偶联受体5(LGR5)染色模式。11名健康受试者、7名林奇综合征患者、4名FAP患者和1名MUTYH相关息肉综合征患者在常规筛查或监视结肠镜检查中进行了活检。石蜡包埋切片用免疫组织化学方法检测隐窝染色。干细胞数量通过使用LGR5和其他蛋白的抗体对分离的隐窝进行免疫荧光染色来估计。与健康受试者、林奇综合征和MUTYH相关息肉综合征受试者相比，FAP受试者隐窝中的LGR5+干细胞数量更多。大多数FAP患者的隐窝内含有LGR5+细胞，位于隐窝下部的1/3以上。这些发现支持一种模型，在该模型中，APC的一个副本失活会导致FAP患者结肠隐窝中LGR5+干细胞数量增加，其中许多是异位的。过多和异位的LGR5+干细胞可能会导致分裂细胞的增殖区扩大，更有可能发生突变，从而导致FAP中观察到的腺瘤加速发展。
Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer (CRC) syndrome characterized by accelerated adenoma development due to inherited (or de novo) mutations in the APC regulator of WNT signaling pathway (APC) gene. The mechanism underlying this accelerated polyp development in subjects with FAP has not been defined. Given that LGR5+ stem cells drive crypt cell proliferation, we hypothesized that FAP crypts would demonstrate aberrant leucine-rich repeat–containing G-protein–coupled receptor 5 (LGR5) staining patterns. Biopsies were taken from 11 healthy subjects, 7 subjects with Lynch syndrome, 4 subjects with FAP, and 1 subject with MUTYH-associated polyposis syndrome during routine screening or surveillance colonoscopy. Crypt staining was evaluated by immunohistochemistry of paraffin-embedded tissue sections. Stem cell numbers were estimated by immunofluorescence staining of isolated crypts using antibodies against LGR5 and other proteins. Subjects with FAP exhibited a greater number of LGR5+ stem cells in their crypts than healthy subjects and subjects with Lynch syndrome and MUTYH-associated polyposis syndrome. Most crypts of subjects with FAP harbored LGR5+ cells located above the lower third of the crypts. These findings support a model in which inactivation of one copy of APC leads to increased numbers of LGR5+ stem cells, many of which are ectopic, in colon crypts of subjects with FAP. Overabundant and ectopic LGR5+ stem cells could lead to an expanded proliferative zone of dividing cells more likely to develop mutations that would contribute to the accelerated adenoma development observed in FAP.
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影响因子：
11.2
作者：
Boman, Bruce M.;Fields, Jeremy Z.;Runquist, Olaf A.
通讯作者：
Runquist, Olaf A.
影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
24.5
作者：
Reynolds A;Wharton N;Parris A;Mitchell E;Sobolewski A;Kam C;Bigwood L;El Hadi A;Münsterberg A;Lewis M;Speakman C;Stebbings W;Wharton R;Sargen K;Tighe R;Jamieson C;Hernon J;Kapur S;Oue N;Yasui W;Williams MR
通讯作者：
Williams MR
影响因子：
64.5
作者：
Powell AE;Wang Y;Li Y;Poulin EJ;Means AL;Washington MK;Higginbotham JN;Juchheim A;Prasad N;Levy SE;Guo Y;Shyr Y;Aronow BJ;Haigis KM;Franklin JL;Coffey RJ
通讯作者：
Coffey RJ
影响因子：
46.9
作者：
通讯作者：
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