结肠癌肝转移中癌症干细胞的特征分析
Characterization of Cancer Stem Cells in Colon Adenocarcinoma Metastasis to the Liver.
作者信息
Humphries Hugo N, Wickremesekera Susrutha K, Marsh Reginald W, Brasch Helen D, Mehrotra Shreeja, Tan Swee T, Itinteang Tinte
机构信息
Gillies McIndoe Research Institute, Wellington, New Zealand.
Upper Gastrointestinal, Hepatobiliary and Pancreatic Section, Department of General Surgery, Wellington Regional Hospital, Wellington, New Zealand.
出版信息
Front Surg. 2018 Jan 22;4:76. doi: 10.3389/fsurg.2017.00076. eCollection 2017.
BACKGROUND
Fifty percent of colorectal cancer (CRC) patients develop liver metastasis. This study identified and characterized cancer stem cells (CSCs) within colon adenocarcinoma metastasis to the liver (CAML).
METHODS
3,3-Diaminobenzidine immunohistochemical (IHC) staining was performed on nine CAML samples for embryonic stem cell (ESC) markers OCT4, SOX2, NANOG, c-Myc, and KLF4. Immunofluorescence (IF) IHC staining was performed to investigate coexpression of two markers. NanoString mRNA expression analysis and colorimetric hybridization (CISH) were performed on four snap-frozen CAML tissue samples for transcript expression of these ESC markers. Cells stained positively and negatively for each marker by IHC and CISH staining were counted and analyzed.
RESULTS
3,3-Diaminobenzidine IHC staining, and NanoString and CISH mRNA analyses demonstrated the expression of OCT4, SOX2, NANOG, c-Myc, and KLF4 within in all nine CAML samples, except for SOX2 which was below detectable levels on NanoString mRNA analysis. IF IHC staining showed the presence of a SOX2/NANOG/KLF4/c-Myc/OCT CSC subpopulation within the tumor nests, and a SOX2/NANOG/KLF4/c-Myc/OCT4 CSC subpopulation and a SOX2/NANOG/KLF4/c-Myc/OCT4 CSC subpopulation within the peritumoral stroma.
CONCLUSION
The novel finding of three CSC subpopulations within CAML provides insights into the biology of CRC.
背景
50%的结直肠癌（CRC）患者会发生肝转移。本研究鉴定并表征了结肠腺癌肝转移（CAML）中的癌症干细胞（CSC）。
方法
对9个CAML样本进行3,3 - 二氨基联苯胺免疫组织化学（IHC）染色，检测胚胎干细胞（ESC）标志物OCT4、SOX2、NANOG、c - Myc和KLF4。进行免疫荧光（IF）IHC染色以研究两种标志物的共表达。对4个速冻的CAML组织样本进行NanoString mRNA表达分析和比色原位杂交（CISH），检测这些ESC标志物的转录表达。对通过IHC和CISH染色每种标志物呈阳性和阴性染色的细胞进行计数和分析。
结果
3,3 - 二氨基联苯胺IHC染色、NanoString和CISH mRNA分析表明，除SOX2在NanoString mRNA分析中低于可检测水平外，所有9个CAML样本中均表达OCT4、SOX2、NANOG、c - Myc和KLF4。IF IHC染色显示肿瘤巢内存在SOX2/NANOG/KLF4/c - Myc/OCT CSC亚群，肿瘤周围基质内存在SOX2/NANOG/KLF4/c - Myc/OCT4 CSC亚群和SOX2/NANOG/KLF4/c - Myc/OCT4 CSC亚群。
结论
在CAML中发现三个CSC亚群这一新颖发现为CRC生物学研究提供了见解。
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