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

Authors

Bruce M. Boman, Thomas Jefferson UniversityFollow
Vignesh Viswanathan
Caroline O B Facey
Jeremy Z Fields
James W Stave

Document Type

Article

Publication Date

3-20-2023

Comments

This article is the author’s final published version in Cancer Biology and Therapy, Volume 24, Issue 1, March 2023 Article number 2195363.

The published version is available at https://doi.org/10.1080/15384047.2023.2195363. Copyright © Boman et al.

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 (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.

Recommended Citation

Boman, Bruce M.; Viswanathan, Vignesh; Facey, Caroline O B; Fields, Jeremy Z; and Stave, James W, "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" (2023). Kimmel Cancer Center Faculty Papers. Paper 98.
https://jdc.jefferson.edu/kimmelccfp/98

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

37005380

Language

English