CD133: beyond a cancer stem cell biomarker

Abstract

CD133 (prominin-1), a pentaspan membrane glycoprotein, is one of the most well-characterized biomarkers used for the isolation of cancer stem cells (CSCs). The presence of CSCs is one of the main causes of tumour reversal and resilience. Accumulating evidence has shown that CD133 might be responsible for CSCs tumourigenesis, metastasis and chemoresistance. It is now understood that CD133 interacts with the Wnt/β-catenin and PI3K-Akt signalling pathways. Moreover, CD133 can upregulate the expression of the FLICE-like inhibitory protein (FLIP) in CD133-positive cells, inhibiting apoptosis. In addition, CD133 can increase angiogenesis by activating the Wnt signalling pathway and increasing the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin-8. Therefore, CD133 could be considered to be an 'Achilles' heel' for CSCs, because by inhibiting this protein, the signalling pathways that are involved in cell proliferation will also be inhibited. By understanding the molecular biology of CD133, we can not only isolate stem cells but can also utilise it as a therapeutic strategy. In this review, we summarise new insights into the fundamental cell biology of CD133 and discuss the involvement of CD133 in metastasis, metabolism, tumourigenesis, drug-resistance, apoptosis and autophagy.

Cancer Stem Cell Target Labeling and Efficient Growth Inhibition of CD133 and PD-L1 Monoclonal Antibodies Double Conjugated with Luminescent Rare-Earth Tb3+ Nanorods

“…Terbium orthophosphate monohydrate (TbPO 4 •H 2 O): Tb(NO 3 ) 3 •5H 2 O (Sigma, 99.9 %) was added to NH 4 H 2 PO 4 solution (Merck) in the presence of polyethylene glycol 2000 (PEG-2000) and stirred for 3-12 h. The pH of the obtained solution was adjusted in the range of 4-12 by adding 10% NaOH solution before incubating at 200 • C for 24 h. The product (TbPO 4 •H 2 O) was centrifuged at 5900 rpm and washed with ddH 2 O before drying at 60 • C for 5-10 h. The nanomaterial was then coated with silica through a hydrolysis reaction with tetra ethyl orthosilicate (TEOS) (Aldrich, 99.99%). Briefly, TbPO 4 •H 2 O was added to a mixture solution containing TEOS, ethanol, acetic acid, and water and stirred for 15 min (TbPO 4 /TEOS molar ratio of 1:0.2). The solution was then centrifuged and washed three times with 33% ethanol solution.…”

“…The solution was then centrifuged and washed three times with 33% ethanol solution. Glycerol solution (0.5 mL) was added to a hydrous mixture of ethanol containing TbPO 4 •H 2 O coated silica (TbPO 4 •H 2 O@silica) and stirred for 30 min. 3-aminopropyl trimethoxy silane (APTMS) was dispersed in ethanol before being mixed with TbPO 4 •H 2 O@silica solution (TbPO 4 •H 2 O@silica/APTMS molar ratio of 1:0.2) and stirred for 15 min to functionalize the surface with -NH 2 .…”

“…Glycerol solution (0.5 mL) was added to a hydrous mixture of ethanol containing TbPO 4 •H 2 O coated silica (TbPO 4 •H 2 O@silica) and stirred for 30 min. 3-aminopropyl trimethoxy silane (APTMS) was dispersed in ethanol before being mixed with TbPO 4 •H 2 O@silica solution (TbPO 4 •H 2 O@silica/APTMS molar ratio of 1:0.2) and stirred for 15 min to functionalize the surface with -NH 2 . The TbPO 4 •H 2 O@silica-NH 2 (TM) materials were washed two times with ethanol, two times with ddH 2 O, and finally dispersed in phosphate buffer saline (PBS) (1X, pH 7).…”

“…The TbPO 4 •H 2 O@silica-NH 2 nanomaterial in sodium phosphate solution was gently vortexed before adding 0.5% glutaraldehyde solution in a ratio of 1:0.5 (v/v) and mixed for 1 h at room temperature (RT) to disperse completely. The mixture was centrifuged and washed three times with PBS solution to remove glutaraldehyde.…”

“…The mixture was centrifuged and washed three times with PBS solution to remove glutaraldehyde. Then, 40 µg of CD133 antibodies (Thermo Fisher, Invitrogen, Carlsbad, CA, USA) was added into the 400 µL glutaraldehyde pre-activated TbPO 4 •H 2 O@silica-NH 2 and incubated at 37 • C for 30 min. After incubation, the suspension was centrifuged at 6000 rpm for 5 min at 4 • C; the supernatant was retained to determine the amount of unconjugated antibodies in the combined efficiency study.…”