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Microbes & Immunity The feature of bladder cancer stem cells

Hoechst 33342. They uncovered a distinct population The self-renewal of BCSCs is driven by a multitude of
of cells that exhibited lower staining intensity compared signaling pathways, such as Hedgehog, Notch, WNT, TGF-
to the majority of other cells. This unique cell population β, BMI1, KMT1A-GATA3-STAT3, and Hippo (Figure 2).
was named side population (SP) cells, and it possessed In-depth research into the self-renewal mechanisms of
characteristics typical of stem cells. ABCG2 belongs to the BCSCs is advantageous for elucidating the etiology of BC
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ABC superfamily and serves as a specific marker for SP cells. and identifying novel therapeutic targets.
ABC proteins have the capability to efflux dyes from within
the cells, resulting in lower staining intensity in SP cells. 3.3.1. Hedgehog pathway
Hepburn et al. at the Northern Institute for Cancer Research The Hedgehog pathway, known for its evolutionary
at Newcastle University in the United Kingdom conducted conservation, plays a crucial role in embryonic development
a study on the expression of ABCG2 in 148 samples of and tissue formation. In an adult, this pathway is typically
NMIBC. The expression of ABCG2 in SP cells was found to inactive, only becoming activated during wound healing
be three times higher than in non-SP cells. 58 and tissue repair process (Figure 3).
To investigate the characteristics of SP cells in BC, In 2014, a study conducted by Shin et al. at Stanford
researchers led by Zhao-Feng Ning at Sun Yat-sen University established a BC mouse model and isolated
University used the Hoechst 33342 dye to isolate cells SHH and SHH cells through flow-activated cytometric
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with lower staining intensity from the human BC cell line sorting from BC lesions at the CIS stage. Subsequent
T24. SP cells accounted for 34.7% of the total population experiments in mice revealed that only SHH cells
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in T24 cells. These SP cells exhibited a six-fold increase exhibited tumorigenic capability across different
in tumorigenic potential compared to non-SP cells,
concomitant with a significant upregulation of ABCG2 dilution gradients. SHH, a critical component of the
expression. In a separate study, researchers led by Jun Hedgehog pathway, engages in downstream signaling by
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Jun She at Xi’an Jiaotong University have identified that binding to the transmembrane protein receptor Patched
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SP cells accounted for 1.6% of the total SW780 cells (PTCH). This observation suggests that during the
through DyeCycle Violet staining. The gradient dilution initial stage of BC formation, heightened expression
experiments conducted in mouse models revealed that of the SHH ligand leads to excessive activation of the
SP cells exhibited a tumorigenic capacity 10 times higher downstream Hedgehog pathway, thereby promoting BC
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than non-SP cells . The presence and proportion of SP cell proliferation and transition toward more aggressive
cells vary among different cell lines, resulting in varying phenotypes.
tumorigenic abilities across different BC cell populations. Through transcriptome analysis of BCMab1 CD44
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Therefore, a comprehensive patient profile assessment is BCSCs and BCMab1 CD44 BCNSCs, we observed that
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imperative when considering the therapeutic targeting of high expression levels of SHH, the transmembrane
SP cells in BC treatment strategies. receptor Smoothened (SMO), and the nuclear transcription
3.2.8. CD24 factor Gli1 in BCSCs. In addition, PTCH1 expression
was detected in BCMab1 CD44 BCSCs. Notably, Gli1
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Researchers led by Akira Ooki at Johns Hopkins University expression in BCSCs was three times higher than that in
isolated CD24 and CD24 high cells from patient-derived BCNSCs. Furthermore, immunohistochemistry (IHC)
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xenograft tumors utilizing magnetic-activated cell sorting. results revealed predominant nuclear localization of
In the sphere formation assay, CD24 high cells exhibited an Gli1 in BCMab1 CD44 BCSCs, further supported by
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approximately one-fold increase in the number of spheroids immunoblotting data demonstrating high expression levels
compared to CD24 cells. Furthermore, in mouse models, of SHH, activated SHH, and Gli1 in these cells. Collectively,
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CD24 high cells formed larger tumors than CD24 cells. these findings suggest that the Hedgehog pathway is in an
low
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These findings suggest that CD24 contributes to the self- activated state within BCSCs. 29
renewal capacity of BCSCs.
Mechanically, the glycosyltransferase GALNT1
3.3. Stemness maintenance mechanism mediates the O-linked glycosylation of SHH to promote its
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The most significant characteristic of BCSCs is their self- activation, which subsequently activates the downstream
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renewal ability. This ability enables them to maintain the transcriptional factor Gli1 within BCSCs. The activated
stem cell pool’s population while giving rise to differentiated Gli1 translocates from the cytoplasm to the cell nucleus,
cells simultaneously. Consequently, even a small number where it induces the transcriptional expression of
of BCSCs can lead to tumor formation, thus contributing Hedgehog target genes. This process ultimately enhances
to the recurrence of BC. the self-renewal capacity of BCSCs.
Volume 1 Issue 1 (2024) 31 doi: 10.36922/mi.2377