Identification of cancer-type specific expression patterns for active aldehyde dehydrogenase (ALDH) isoforms in ALDEFLUOR assay

Zhou, Lei; Sheng, Dandan; Wang, Dong; Ma, Wei; Deng, Qiaodan; Deng, Lu; Liu, Suling

doi:10.1007/s10565-018-9444-y

Cited by 72 publications

(73 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ALDH dim and ESA − cells in MDA-MB-231 and UACC-812 cell lines, which were considered as non-BCSCs, were also sorted from these cell lines. In addition, we did qRT-PCR on sorted BCSCs vs non-BCSCs for mRNA expression of ALDH1A1 which is one of the main contributors to ALDH activity detected by ALDEFLUOR [40]. The data were consistent with ALDEFLUOR assay by which we identified and sorted ALDH bright / ALDH dim cells, i.e., ALDH bright cells expressed higher levels (18-25 fold increase) of ALDH1A1 mRNA than that in ALDH dim cells (Fig.…”

Section: Resultssupporting

confidence: 77%

Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram

Sun

Yang

Toprani³

et al. 2020

Cell Commun Signal

View full text Add to dashboard Cite

Background: The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response. Methods: High aldehyde dehydrogenase activity (ALDH) bright and CD44 + /CD24 − /ESA + cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA). Results: We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The results indicate that DSF/Cu induced a similar extent of IDC in both BCSCs and non-BCSCs and rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. IR and DSF/Cu induced ICD of BCSCs could be partly reversed by pre-treatment of BCSCs with a reactive oxygen species (ROS) scavenger and XBP1s inhibitors. Conclusion: DSF/Cu rendered IR-resistant BCSCs as sensitive as non-BCSCs to IR-induced ICD. Our data demonstrate the potential of IR and DSF/Cu to induce ICD in BCSCs and non-BCSCs leading to robust immune responses against not only differentiated/differentiating breast cancer cells but also BCSCs, the root cause of cancer formation, progression and metastasis.

show abstract

Section: Resultssupporting

confidence: 77%

Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram

Sun

Yang

Toprani³

et al. 2020

Cell Commun Signal

View full text Add to dashboard Cite

show abstract

“…Centroacinar cells have been prospectively isolated on the basis of their high Aldh activity using the live Aldh substrate Aldefluor, which detects several Aldh isoforms (23,24). When cultured under specific conditions in suspension these cells generated pancreatospheres containing endocrine and acinar cells raising the possibility that these cells could carry a similar function in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…In adult zebrafish, CACs generate new β cells following β-cell ablation or partial pancreatectomy (22). In the mouse, they have been prospectively isolated through their high aldhehyde dehydrogenase (Aldh) activity using the Aldefluor reagent that detects several Aldh isoforms (23,24). These cells have been described as both progenitor-like and tumor-initiating cells (TICs) (22,(25)(26)(27) and…”

mentioning

confidence: 99%

Aldh1b1 expression defines progenitor cells in the adult pancreas and is required for Kras-induced pancreatic cancer

Mameishvili

Serafimidis

Iwaszkiewicz

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The presence of progenitor or stem cells in the adult pancreas and their potential involvement in homeostasis and cancer development remain unresolved issues. Here, we show that mouse centroacinar cells can be identified and isolated by virtue of the mitochondrial enzyme Aldh1b1 that they uniquely express. These cells are necessary and sufficient for the formation of self-renewing adult pancreatic organoids in an Aldh1b1-dependent manner. Aldh1b1-expressing centroacinar cells are largely quiescent, self-renew, and, as shown by genetic lineage tracing, contribute to all 3 pancreatic lineages in the adult organ under homeostatic conditions. Single-cell RNA sequencing analysis of these cells identified a progenitor cell population, established its molecular signature, and determined distinct differentiation pathways to early progenitors. A distinct feature of these progenitor cells is the preferential expression of small GTPases, including Kras, suggesting that they might be susceptible to Kras-driven oncogenic transformation. This finding and the overexpression of Aldh1b1 in human and mouse pancreatic cancers, driven by activated Kras, prompted us to examine the involvement of Aldh1b1 in oncogenesis. We demonstrated genetically that ablation of Aldh1b1 completely abrogates tumor development in a mouse model of KrasG12D-induced pancreatic cancer.

show abstract

“…AldeFluor-assay activity would instead be expected to be higher in stem cells, oppositely to our observations. In fact, AldeFluor-assay activity reflects the activity of various aldehyde dehydrogenases [30], whose expression does not necessarily have to be localized in the stem cell population of a tissue. AldeFluor activity was linked to tumor-initiating cells in bladder cancer in a previous publication, but the authors did not investigate the association with KRT14 expression [31].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of UTX/KDM6A Enriches Precursor Cell Populations in Urothelial Cell Cultures and Cell Lines

Lang

Whongsiri

Yılmaz

et al. 2020

Cancers

View full text Add to dashboard Cite

The histone demethylase UTX (gene: KDM6A) directs cell and tissue differentiation during development. Deleterious mutations in KDM6A occur in many human cancers, most frequently in urothelial carcinoma. The consequences of these mutations are poorly understood; plausibly, they may disturb urothelial differentiation. We therefore investigated the effects of UTX siRNA-mediated knockdown in two in vitro models of urothelial differentiation; namely, primary cultures of urothelial epithelial cells treated with troglitazone and PD153035 and the immortalized urothelial cell line HBLAK treated with high calcium and serum. In both models, efficient UTX knockdown did not block morphological and biochemical differentiation. An apparent delay was due to a cytotoxic effect on the cell cultures before the initiation of differentiation, which induced apoptosis partly in a p53-dependent manner. As a consequence, slowly cycling, smaller, KRT14 high precursor cells in the HBLAK cell line were enriched at the expense of more differentiated, larger, proliferating KRT14 low cells. UTX knockdown induced apoptosis and enriched KRT14 high cells in the BFTC-905 papillary urothelial carcinoma cell line as well. Our findings suggest an explanation for the frequent occurrence of KDM6A mutations across all stages and molecular subtypes of urothelial carcinoma, whereby loss of UTX function does not primarily impede later stages of urothelial differentiation, but favors the expansion of precursor populations to provide a reservoir of potential tumor-initiating cells.

show abstract

Identification of cancer-type specific expression patterns for active aldehyde dehydrogenase (ALDH) isoforms in ALDEFLUOR assay

Cited by 72 publications

References 59 publications

Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram

Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram

Aldh1b1 expression defines progenitor cells in the adult pancreas and is required for Kras-induced pancreatic cancer

Knockdown of UTX/KDM6A Enriches Precursor Cell Populations in Urothelial Cell Cultures and Cell Lines

Contact Info

Product

Resources

About