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

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Author(s)Boman, Bruce M.
Author(s)Viswanathan, Vignesh
Author(s)Faceya, Caroline O. B.
Author(s)Fields, Jeremy Z.
Author(s)Stave, James W.
Date Accessioned2023-05-31T14:41:42Z
Date Available2023-05-31T14:41:42Z
Publication Date2023-04-02
Description© 2023 The Author(s). This article was originally published in Cancer Biology & Therapy. The version of record is available at: https://doi.org/10.1080/15384047.2023.2195363
AbstractCD44 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 (n = 10) of malignant colonic tissue and adjacent normal mucosa, using two (IHC & IF) immunostaining approaches. We found that: i) CD44v8–10 is selectively expressed in the normal human colonic SC niche; ii) CD44v8–10 is co-expressed with the SC markers ALDH1 and LGR5 in normal and malignant colon tissues; iii) 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.
SponsorFunding for this study was awarded by The Lisa Dean Moseley Foundation (BB, CF), Cancer B*Ware Foundation (BB), Delaware Bioscience Center for Advanced Technology (BB, VV), The Cawley Center for Translational Cancer Research Fund (BB, VV, CF), Friends of the Helen F. Graham Cancer Center & Research Institute (BB), University of Delaware Department of Biological Sciences (VV), and INBRE NIH/NIGMSGM103446 (BB, VV, CF).
CitationBruce M. Boman, Vignesh Viswanathan, Caroline O. B. Facey, Jeremy Z. Fields & James W. Stave (2023) 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, Cancer Biology & Therapy, 24:1, DOI: 10.1080/15384047.2023.2195363
ISSN1555-8576
URLhttps://udspace.udel.edu/handle/19716/32813
Languageen_US
PublisherCancer Biology & Therapy
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
KeywordsCD44 protein
KeywordsCD44v8-10
KeywordsCD44 variant isoforms
Keywordscancer stem cells
Keywordscolorectal cancer
TitleThe 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
TypeArticle
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