CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation.
BACKGROUND
We investigated whether CD24 (reportedly a stem cell marker and adhesion molecule) was expressed in regenerative mucosa in inflammatory bowel disease (IBD) and whether it could be functionally relevant.


METHODS
CD24 expression was examined in 10 cases of IBD and the relationship of CD24 with Wnt signaling was tested using dominant negative (DN)-TCF4 expression. For functional evaluation, CD24 was 1) cloned and forcibly expressed in HCT116 (which expresses very low levels of CD24) and 2) knocked-down by RNA interference in HT29 (which expresses high levels of CD24). The effect of altered CD24 expression on proliferation/apoptosis, staurosporine-induced apoptosis, colony formation in soft agar, migration, and invasion was examined.


RESULTS
CD24 was not expressed in normal tissue, while 10/10 cases of IBD showed CD24 upregulation. Inhibition of Wnt signaling with DN-TCF4 caused CD24 downregulation. Forced expression of CD24 did not influence cell proliferation, apoptosis, or staurosporine-induced apoptosis but it did significantly enhance colony forming efficiency (P < 0.01). Furthermore, there was increased transwell migration (P < 0.001) and invasion (P < 0.03) and there was increased cell migration in wounding assays. Conversely, knockdown of CD24 reduced transwell migration (P < 0.01) and invasion (P < 0.01) and reduced cell motility in wounding assays. CD24 knockdown did not influence proliferation, apoptosis resistance, or staurosporine-induced apoptosis.


CONCLUSIONS
This is the first study to report upregulation of CD24 in regenerating tissue in IBD. This may be regulated by Wnt signaling and can confer enhanced colony forming ability and enhanced cell motility-features that may be important in tissue healing in the colon.
Ahmed
Mohamed A H
MA
Division of Pathology, School of Molecular Medical Sciences, Queen's Medical Centre Campus, University of Nottingham, UK. mohammed.ilyas@nottingham.ac.uk
Jackson
Darryl
D
Seth
Rashmi
R
Robins
Adrian
A
Lobo
Dileep N
DN
Tomlinson
Ian P M
IP
Ilyas
Mohammad
M
D017209:Apoptosis; D015153:Blotting, Western; D051927:CD24 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000378:metabolism; D003114:Colony-Forming Units Assay; D006801:Humans; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000378:metabolism
D051927:CD24 Antigen; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051153:Wnt Proteins