Page 44 - MI-1-1

Microbes & Immunity The feature of bladder cancer stem cells

Janus kinase 2 (JAK2), thereby promoting the formation of BCSCs. Initially, they uncovered a positive correlation
of the JAK2-STAT3 complex. This complex activation of between METTL3 expression and the tumorigenicity of
STAT3 subsequently induced the expression of TWIST1, BC by manipulating METTL3 levels in CK14 BCSCs in a
+
thereby activating EMT in BC cells. Furthermore, they mouse model. Furthermore, through Gene Ontology (GO)
94
introduced cell cycle-defective phosphatase (p27CK-DD) analysis and m A RNA immunoprecipitation sequencing,
6
into GFP-labeled UMUC3 cells, leading to an increase they posited that METTL3 mediates m A modification
6
in the expression of p27. Subsequent injection of these to suppress TEK/VEGF-A, thereby promoting BC
modified cells into the tail veins of mice facilitated the angiogenesis. Furthermore, EMT is interconnected
95
establishment of a BC model. Through in vivo imaging, with various pathways. The WNT pathway, for instance,
the presence of GFP-positive cells in the tumors allowed promotes EMT by inducing β-catenin translocation into
96
for the identification of metastatic tumor sites. Initially the cell nucleus. Similarly, the Notch pathway induces
exhibiting weak migratory abilities, UMUC3 cells with EMT through interactions with the Smads and NF-κB
97
p27 overexpression developed tumors in the lungs, liver, pathways, while the Hedgehog pathway also contributes
and kidneys of mice, with the lungs displaying the highest to EMT. The components involved in these pathways hold
98
incidence of metastatic tumor cells. Importantly, the promise as potential therapeutic targets for suppressing
introduction of STAT3DN (a dominant negative form of EMT.
STAT3) into p27-overexpressing UMUC3 cells resulted
in a reduction in metastatic tumor formation in the 3.6. Metabolic reprogramming
lungs to a level comparable to that of parental cells. This Compared to normal tissues, cancer cells undergo
94
observation indicates the capacity of P27CK-DD to induce significant alterations in their metabolic pathways. Among
EMT and enhance tumor metastasis, while inhibition of these, the metabolic features of TSCs differ from those of
STAT3 expression could reverse this process, attenuating other cell types. Given their pivotal role in tumor initiation,
migratory abilities. The observed high expression of STAT3 progression, metastasis, and relapse, TSCs represent
in BCSCs suggests its role in promoting EMT through crucial therapeutic targets. Therefore, understanding the
these pathways, thus endowing BC with a heightened metabolic characteristics specific to TSCs and developing
potential for distant metastasis. novel therapies targeting cancer metabolism pathways
hold tremendous potential in the field of cancer research.
3.5.2. OV6
Wang et al. have determined, through experiments in 3.6.1. GD2
+
mice, that OV6 BCSCs exhibit approximately three times Researchers led by Venkatrao Vantaku at Baylor College of
-
higher rates of lung metastasis compared to OV6 BCNSCs. Medicine have revealed elevated levels of GD2 expression
The expression of vimentin (a marker of EMT) in lung in high-grade BC tissues and cell lines (UMUC3 and J82)
metastatic tumors was evaluated using IHC. The results compared to low-grade BC tissues and cell lines (RT4 and
revealed a higher positivity rate for vimentin in OV6 lung 5637), as revealed by high-resolution mass spectrometry
+
tumors, with an average IHC score above five, whereas analysis. Flow cytometry analysis further delineated
99
OV6 lung tumors displayed an average IHC score below that GD2 cells constituted 82.6% of the high-grade cell
-
+
2.5. These findings suggest the potential involvement of line UMUC3, while in the other three cell lines, GD2
28
+
OV6 BCSCs in tumor metastasis through the process of cells were present at levels below 2%. Remarkably, GD2
+
+
EMT. UMUC3 cells exhibited mesenchymal characteristics and
heightened proliferative abilities. Further analysis of GD2
+
3.5.3. METTL3 cells isolated from UMUC-3 cells revealed that 93.2% of
To sustain their growth, solid tumors must initiate these cells exhibited the CD44 high CD24 phenotype,
low
angiogenesis upon reaching a certain size to ensure which corresponds to the phenotype of TSCs. Thus, it is
an adequate oxygen supply while simultaneously postulated that GD2 cells may possess the characteristics
+
facilitating the migration of tumor cells through blood of BCSCs. 99
vessels to nutrient-rich sites. Therefore, a comprehensive Due to the enhanced proliferative capabilities observed
understanding of the angiogenesis mechanism in BC is in GD2 cells, lipid analysis was performed on GD2 and
+
+
crucial for the development of new treatment strategies. GD2 cells in UMUC-3. This analysis revealed elevated
-
Researchers led by Ganping Wang from Sun Yat-sen levels of phosphatidylinositol (PI), phosphatidic acid
University have unveiled the pivotal role of METTL3 in (PA), and cardiolipin (CL), alongside reduced levels of
BCSCs in promoting angiogenesis by regulating TEK and phosphatidylserine (PS), plasma phosphatidylethanolamine
VEGF-A, thereby enhancing the growth and tumorigenicity (pPE), plasma phosphatidylcholine (pPC), sphingomyelin
Volume 1 Issue 1 (2024) 38 doi: 10.36922/mi.2377