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CD44 的 v8-10 变异体同工型在正常人类结肠干细胞龛中选择性表达,并且在肿瘤发展过程中在结肠癌中经常过表达。

The v8-10 variant isoform of CD44 is selectively expressed in the normal human colonic stem cell niche and frequently is overexpressed in colon carcinomas during tumor development.

机构信息

Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, DE, USA.

Department of Biologic Sciences, University of Delaware, Newark, DE, USA.

出版信息

Cancer Biol Ther. 2023 Dec 31;24(1):2195363. doi: 10.1080/15384047.2023.2195363.

DOI:10.1080/15384047.2023.2195363
PMID:37005380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10072056/
Abstract

CD44 protein and its variant isoforms are expressed in cancer stem cells (CSCs), and various CD44 isoforms can have different functional roles in cells. Our goal was to investigate how different CD44 isoforms contribute to the emergence of stem cell (SC) overpopulation that drives colorectal cancer (CRC) development. Specific CD44 variant isoforms are selectively expressed in normal colonic SCs and become overexpressed in CRCs during tumor development. We created a unique panel of anti-CD44 rabbit genomic antibodies to 16 specific epitopes that span the entire length of the CD44 molecule. Our panel was used to comprehensively investigate the expression of different CD44 isoforms in matched pairs ( = 10) of malignant colonic tissue and adjacent normal mucosa, using two (IHC & IF) immunostaining approaches. We found that: ) CD44v8-10 is selectively expressed in the normal human colonic SC niche; ) CD44v8-10 is co-expressed with the SC markers ALDH1 and LGR5 in normal and malignant colon tissues; ) colon carcinoma tissues frequently (80%) stain for CD44v8-10 while staining for CD44v6 was less frequent (40%). Given that CD44v8-10 expression is restricted to cells in the normal human colonic SC niche and CD44v8-10 expression progressively increases during CRC development, CD44v8-10 expression likely contributes to the SC overpopulation that drives the development and growth of colon cancers. Since the CD44 variant v8-10 epitope is located on CD44's extracellular region, it offers great promise for targeted anti-CSC treatment approaches.

摘要

CD44 蛋白及其变异体同工型在癌症干细胞 (CSC) 中表达,并且各种 CD44 同工型在细胞中可能具有不同的功能作用。我们的目标是研究不同的 CD44 同工型如何促成驱动结直肠癌 (CRC) 发展的干细胞 (SC) 过度增殖的出现。特定的 CD44 变体同工型在正常结肠 SC 中特异性表达,并在肿瘤发展过程中在 CRC 中过度表达。我们创建了一组针对 CD44 分子全长的 16 个特异性表位的独特兔基因组抗 CD44 抗体。我们的小组使用两种(免疫组织化学和免疫荧光)免疫染色方法,在恶性结肠组织和相邻正常粘膜的 10 对匹配对中全面研究不同 CD44 同工型的表达。我们发现:(1)CD44v8-10 选择性地在正常人类结肠 SC 生态位中表达;(2)CD44v8-10 与 SC 标记物 ALDH1 和 LGR5 在正常和恶性结肠组织中共同表达;(3)结肠癌组织经常(80%)染色 CD44v8-10,而染色 CD44v6 则较少(40%)。鉴于 CD44v8-10 的表达仅限于正常人类结肠 SC 生态位中的细胞,并且 CD44v8-10 的表达在 CRC 发展过程中逐渐增加,CD44v8-10 的表达可能有助于驱动结肠癌发生和生长的 SC 过度增殖。由于 CD44 变体 v8-10 表位位于 CD44 的细胞外区,因此它为靶向抗 CSC 治疗方法提供了巨大的希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/76afb8a3a712/KCBT_A_2195363_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/1111e608d103/KCBT_A_2195363_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/150062bda978/KCBT_A_2195363_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/c76eddd1299e/KCBT_A_2195363_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/c928e3d27451/KCBT_A_2195363_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/a82bd08e7d36/KCBT_A_2195363_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/76afb8a3a712/KCBT_A_2195363_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/1111e608d103/KCBT_A_2195363_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/150062bda978/KCBT_A_2195363_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/c76eddd1299e/KCBT_A_2195363_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/c928e3d27451/KCBT_A_2195363_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/a82bd08e7d36/KCBT_A_2195363_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a9/10072056/76afb8a3a712/KCBT_A_2195363_F0006_OC.jpg

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