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Microbes & Immunity                                                  The feature of bladder cancer stem cells



            for 67LR /CK17 /CEACAM6 cells from the human BC    lines was determined to be 7.4 ± 1.6%. Nude mouse
                         +
                   +
                                    - 
            cell line SW780 and BC samples. Through experiments   xenotransplantation experiments demonstrated that
            conducted in mouse models, they demonstrated that these   ALDH1A1  BC cells exhibited 100  times tumorigenic
                                                                        +
            cells exhibited 5 – 10 times greater tumorigenic potential   potential  compared  to  ALDH1A1 BC  cells.  Suppression
                                                                                           - 
            compared to the remaining cells.  In summary, these   of ALDH1A1 expression remarkably decreased the
                                        41
            findings support the use of 67LR /CK17 /CEACAM6 as   tumorigenicity of BCSCs. Moreover, ALDH1A1  BC cells
                                             +
                                                                                                     +
                                                        - 
                                       +
            biomarkers for the isolation and identification of BCSCs.  were capable of continuous passage and transplantation in
                                                               vivo, differentiating into heterogeneous cell populations. 31
                        +
            3.2.3. BCMab1 /CD44 +
                                                               3.2.6. OV6
            Our group has successfully screened a highly specific
            monoclonal antibody called BCMab1 using the hybridoma   The epithelial marker OV6 has been identified as a potential
            technique. BCMab1 specifically targets aberrantly   marker for TSCs in various epithelial malignancies, such
            glycosylated integrin α3β1 on BC, whose expression levels   as esophageal squamous cell carcinoma and hepatocellular
            were found to be positively correlated with the pathological   carcinoma,  with  extensive  exploration  of  its  role  in
                                                                                     55
            stage and grade of BC.  Through co-expression with CD44,   hepatocellular carcinoma.  Furthermore, OV6 has
                             29
                                                                                                            56
            our group isolated BCMab1 CD44  BCSCs from patient   emerged as a new prognostic marker of colorectal cancer.
                                        +
                                   +
            BC samples, with the proportion of these BCSCs ranging   Recent studies have indicated high expression of OV6 in
            from 3 – 5% of total cells. Subsequently, when these BC   BC patient samples, with OV6 expression levels positively
            cell subtypes were injected subcutaneously into non-obese   correlated with disease progression and poor prognosis.
            diabetic/severe  combined  immunodeficiency  (NOD/   Researchers led by Kai-Jian Wang from the Second
                                                      +
                                                +
            SCID) mice, it was observed that 10 BCMab1 CD44  cells   Military Medical University investigated the relationship
                                                 -
            exhibited tumorigenic ability, while BCMab1 CD44 cells   between OV6  and BCSCs.  Initially,  flow cytometry
                                                      - 
            required at least 1×10   cells to form tumors.  These   revealed OV6 expression in 2.63% of UMUC-3 and 3.23%
                               5
                                                   29
            findings demonstrate that BCMab1 CD44  BC cells possess   of J82 cells. In single-cell sphere formation assays, OV6  BC
                                       +
                                             +
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            tumorigenic capability, confirming their characteristic   cells formed 100 – 150 spheroids, whereas OV6 cells formed
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            features as BCSCs.                                 fewer than 50, suggesting a stronger self-renewal capacity
                                                                          28
                                                                     +
            3.2.4. CD90 /CK14 +                                in OV6  cells.  Through gradient dilution transplantation
                      +
                                                               experiments, they found that the estimated tumorigenic
            CD90, also known as Thy-1, is a 25 – 37  kDa       efficiency of OV6  cells derived from UMUC-3 was 1 in
                                                                             +
            glycosylphosphatidylinositol (GPI)-anchored glycoprotein   14,378, whereas the estimated tumorigenic efficiency of
            expressed in various cell types, including hematopoietic   OV6 cells was 1 in 199,834. In the case of J82-derived cells,
                                                                   - 
            stem cells, activated microvascular endothelial cells, and   the estimated tumorigenic efficiency of OV6  cells was 1
                                                                                                   +
            fibroblasts. It plays a role in cell adhesion, migration, and   in 27,195, whereas the estimated tumorigenic efficiency of
            fibrosis. Volkmer et al. at Stanford University discovered   OV6 cells was 1 in 199,834. These findings indicated that
                                                                   - 
                                                         53
            that CK14  BC cells exhibited high expression of CD90.    OV6   cells  exhibited  a significantly  higher  tumorigenic
                    +
                                                                   +
            The experimental results using mouse models revealed   potential compared to OV6 cells.
                                                                                     - 
            that CD90 CK14  BC cells demonstrated 17 times greater   Subsequently,  OV6 CD44 ,  OV6 CD44 ,  and
                    +
                         +
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                                                                                                      -
                                                                                   +
                                                                                         +
            tumorigenic potential compared to CD90 CK14  BC cells.   OV6 CD44  cells were isolated from UMUC-3  cells and
                                                 low
                                            -
                                                                   -
                                                                        +
            This evidence indicates that CD90 CK14  cells possess the   subjected to experiments involving mouse models. The
                                       +
                                            +
            characteristic features of BCSCs. 53
                                                               absence of CD44 reduced the estimated tumorigenic
            3.2.5. ALDH1A1                                     efficiency from 1 in 10,605 to 1 in 17,966. Similarly, in the
                                                               two groups of CD44  cells, the absence of OV6 reduced
                                                                                +
            Acetaldehyde dehydrogenase 1 belongs to the ALDH   the estimated tumorigenic efficiency from 1 in 10,605 to
            superfamily  and  plays  a  role  in the differentiation  and   1 in 97,286. Clearly, compared to CD44, the expression
            gene  expression  of  various  tissues.  Moreover,  ALDH1  is   or absence of OV6 exerted a greater impact on the
            essential for the growth and differentiation of adult tissue   tumorigenic capability of BC cells.  Therefore, OV6  cells
                                                                                                         +
                                                                                           28
            stem cells and TSCs. It is currently a hot topic in the study   potentially represent a subset of BCSC.
            of TSC markers, especially as a marker for breast TSCs. 54
              Su  et al. used ALDEFLUOR and flow-activated     3.2.7. Side population cells
            cytometry to isolate ALDH1A1 cells from three      In 1996, researchers at the Massachusetts Institute of
                                         +
            human BC cell lines (HTB-2, HTB-4, and HTB-9).     Technology (MIT), led by Goodell  et al., conducted flow
            The average percentage of this subset in the three cell   cytometric analysis by staining cells with the DNA dye
            Volume 1 Issue 1 (2024)                         30                               doi: 10.36922/mi.2377
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