Cancer stem cell markers in common cancers – therapeutic implications

Klonisch, Thomas; Wiecheć, Emilia; Hombach‐Klonisch, Sabine; Ande, Sudharsana Rao; Wesselborg, Sebastian; Schulze‐Osthoff, Klaus; Łos, Marek

doi:10.1016/j.molmed.2008.08.003

Cited by 356 publications

(308 citation statements)

References 120 publications

(93 reference statements)

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“…Of note, these markers are reported in HSCs and various CSCs. 4,5,32 The superficial bladder wall marker CK-20 was also detected in RT4P and blebbishields (Figure 8b).…”

Section: Resultsmentioning

confidence: 93%

“…4 Although the CSCs between cancer types differ in marker expression, most CSCs share common features such as the ability to form spheres, dye exportation, drug resistance, heterogeneity, and tumorigenicity. [4][5][6][7][8] However, not all CSCs exhibit all of these properties. Hence, tumorigenicity is considered as the important criteria for CSC characterization.…”

mentioning

confidence: 99%

“…8,11 CSCs have been implicated in the resistance to therapeutic interventions in various cancers. 4,8 However, it is not completely understood whether the resistance and relapse of cancers are due to insufficient therapy or due to the intrinsic survival mechanisms of CSCs. Here, we show that cancer cells with apoptotic characteristics survive by evoking a novel emergency program involving fusion of apoptotic blebs to form spherical structures, which we term blebbishields.…”

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confidence: 99%

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Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis

et al. 2012

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Caspases mediate apoptosis and have also been implicated in stem-cell biology. How caspases are linked to stem-cell biology is not known. Here, we show that the apoptotic blebs of cancer cells fuse together to form novel structures called 'blebbishields'. Blebbishields form spheres by fusion. Both blebbishield formation and sphere formation involve active caspases and N-linked glycosylation. Sphere formation is enhanced by acidic pH and is counteracted by inhibitors of proton pump, caspases, and cholesterol. The blebbishields from VEGFR2 High cells are capable of enhanced sphere formation. Blebbishields express transiently downregulated stem-cell markers and the sphere-forming blebbishield-derived cells are tumorigenic. Our study demonstrates that the cancer stem cells can survive after apoptosis by blebbishield formation and subsequent sphere formation.

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“…Of note, these markers are reported in HSCs and various CSCs. 4,5,32 The superficial bladder wall marker CK-20 was also detected in RT4P and blebbishields (Figure 8b).…”

Section: Resultsmentioning

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis

et al. 2012

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“…Thus, the characterization of the CSC population is critical to develop more specific therapeutic strategies for cancer treatment 3. Currently, the routine methods using displayed surface makers are widely applied to target and characterize CSCs in different types of tumors 4. However, the expressions of surface markers are controversial in different types of tumors, which may even cause conflicting results in different of researches 5.…”

Section: Introductionmentioning

confidence: 99%

Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity

et al. 2018

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The characterization of cancer stem‐like cells (CSCs) has profound implications for elucidating cancer biology and developing treatment strategies. Although surface markers are already used to identify CSCs, the expression of these markers is controversially linked to the phenotypes in different types of tumors and does not represent all functionally relevant of CSCs. Very recently, hyperactive HIF‐1α/glycolysis metabolic pathway is recognized as a master regulator of CSCs. In this study, a near‐infrared fluorescent small‐molecule, IR‐780, is identified for the exclusive characterization of human CSCs through the HIF‐1α/glycolysis dependent mitochondrial transporter ABCB10's activity. The results identified for the first time that ABCB10 is involved in the preferential uptake of IR‐780 in CSCs, which is regulated by HIF‐1α via the direct interaction with the binding site of ABCB10 gene promoter region. In addition, IR‐780 is demonstrated to conjugate with anticancer drug 5‐fluorouracil to act as a potential drug delivery carrier for CSC‐targeted therapy. Thus, the studies provide a new rational approach independent of surface markers to characterize CSCs via small‐molecule‐based imaging of HIF‐1α/glycolysis hyperactive metabolic pathway dependent mitochondrial transporter's activity, which holds promise for the further development of CSCs targeted diagnostic and therapeutic strategies.

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“…4 The existence of CSCs was later also reported in neural, 5 colon, 6 pancreatic, 7 head and neck, 8 prostate 9 and other cancers. 10,11 CSCs remain largely resistant to the majority of current anticancer therapeutics (i.e. chemotherapeutic drugs) even though such therapies kill differentiated cancer cells that form the bulk of the tumor.…”

Section: Introductionmentioning

confidence: 99%

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1

et al. 2015

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Cancer stem-like cells (CSCs) are a rare subpopulation of cancer cells capable of propagating the disease and causing cancer recurrence. In this study, we found that the cellular localization of PKB/Akt kinase affects the maintenance of CSCs. When Akt tagged with nuclear localization signal (Akt-NLS) was overexpressed in SKBR3 and MDA-MB468 cells, these cells showed a 10-15% increase in the number of cells with CSCs enhanced ALDH activity and demonstrated a CD44 CHigh /CD24 ¡Low phenotype. This effect was completely reversed in the presence of Aktspecific inhibitor, triciribine. Furthermore, cells overexpressing Akt or Akt-NLS were less likely to be in G0/G1 phase of the cell cycle by inactivating p21 Waf1/Cip1 and exhibited increased clonogenicity and proliferation as assayed by colony-forming assay (mammosphere formation). Thus, our data emphasize the importance the intracellular localization of Akt has on stemness in human breast cancer cells. It also indicates a new robust way for improving the enrichment and culture of CSCs for experimental purposes. Hence, it allows for the development of simpler protocols to study stemness, clonogenic potency, and screening of new chemotherapeutic agents that preferentially target cancer stem cells. Summary: The presented data, (i) shows new, stemness-promoting role of nuclear Akt/PKB kinase, (ii) it underlines the effects of nuclear Akt on cell cycle regulation, and finally (iii) it suggests new ways to study cancer stem-like cells.

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Cancer stem cell markers in common cancers – therapeutic implications

Cited by 356 publications

References 120 publications

Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis

Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis

Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1

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Cancer stem cell markers in common cancers – therapeutic implications

Cited by 356 publications

References 120 publications

Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis

Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis

Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity

Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21Waf1/Cip1and p27kip1

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Nuclear localized Akt enhances breast cancer stem-like cells through counter-regulation of p21^Waf1/Cip1and p27^kip1