Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells

Doherty, Rachel; Haywood-Small, Sarah; Sisley, Karen; Cross, Neil

doi:10.1016/j.bbrc.2011.10.010

Cited by 33 publications

(33 citation statements)

References 30 publications

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“…Thus, our study establishes a robust mouse model and FACSbased analysis to study metastases of cancer cells and stem-like cancer cells to bone. Our findings are in agreement with the reported studies in breast cancer (36)(37)(38) and prostate cancer (39,40), which suggest that rare subsets of cancer cells are sufficient to initiate metastases to distant organs.…”

Section: Discussionsupporting

confidence: 93%

“…Aldehyde dehydrogenase 1 (ALDH1) is a detoxifying enzyme responsible for the oxidation of intracellular aldehydes and has emerged as an ideal marker for isolation of stem-like cells from heterogeneous tumors (32)(33)(34)(35). As the ALDH activity is increased in cancer stem cell populations isolated from multiple myeloma, acute myeloid leukemia (15), breast cancer lung, head and neck, gastric and colorectal cancers and recently in prostate cancer (36)(37)(38)(39)(40)(41)(42)(43)(44)(45), it is therefore considered as a reliable marker for isolation of cancer stem cells. Importantly, isolated ALDH high stem-like prostate cancer cells initiate growth of tumors in orthotopic mouse models (40).…”

Section: Introductionmentioning

confidence: 99%

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Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow

et al. 2016

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Bone metastasis is a leading cause of morbidity and mortality in prostate cancer. While cancer stem-like cells have been implicated as a cell of origin for prostate cancer metastasis, the pathways that enable metastatic development at distal sites remain largely unknown. In this study, we illuminate pathways relevant to bone metastasis in this disease. We observed that cyclin A1 (CCNA1) protein expression was relatively higher in prostate cancer metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase (CYP19A1), a key enzyme that directly regulates the local balance of androgens to estrogens. Cyclin A1 overexpression in the stem-like ALDH high subpopulation of PC3M cells, one model of prostate cancer, enabled bone marrow integration and metastatic growth. Further, cells obtained from bone marrow metastatic lesions displayed self-renewal capability in colonyforming assays. In the bone marrow, cyclin A1 and aromatase enhanced local bone marrow-releasing factors, including androgen receptor, estrogen and matrix metalloproteinase MMP9 and promoted the metastatic growth of prostate cancer cells. Moreover, ALDH high tumor cells expressing elevated levels of aromatase stimulated tumor/host estrogen production and acquired a growth advantage in the presence of host bone marrow cells. Overall, these findings suggest that local production of steroids and MMPs in the bone marrow may provide a suitable microenvironment for ALDH high prostate cancer cells to establish metastatic growths, offering new approaches to therapeutically target bone metastases. Cancer Res; 76(8); 2453-64. Ó2016 AACR.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow

et al. 2016

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“…15 TICs are hard to detect and separate even with the most sensitive techniques due to genetic similarity with other tumor cells. Furthermore, methods that rely on specific surface markers for detection are hampered by the lack of a defined genetic fingerprint of target cells even from the same tissue; 16 thus, a pure population of specific cells still cannot be isolated.…”

Section: Introductionmentioning

confidence: 99%

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

et al. 2016

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We designed a new microfluidic device that uses pillars on the same order as the diameter of a cell (20 lm) to isolate and enrich rare cell samples from background. These cell-scale microstructures improve viability, trapping efficiency, and throughput while reducing pearl chaining. The area where cells trap on each pillar is small, such that only one or two cells trap while fluid flow carries away excess cells. We employed contactless dielectrophoresis in which a thin PDMS membrane separates the cell suspension from the electrodes, improving cell viability for off-chip collection and analysis. We compared viability and trapping efficiency of a highly aggressive Mouse Ovarian Surface Epithelial (MOSE) cell line in this 20 lm pillar device to measurements in an earlier device with the same layout but pillars of 100 lm diameter. We found that MOSE cells in the new device with 20 lm pillars had higher viability at 350 V RMS , 30 kHz, and 1.2 ml/h (control 77%, untrapped 71%, trapped 81%) than in the previous generation device (untrapped 47%, trapped 42%). The new device can trap up to 6 times more cells under the same conditions. Our new device can sort cells with a high flow rate of 2.2 ml/h and throughput of a few million cells per hour while maintaining a viable population of cells for off-chip analysis. By using the device to separate subpopulations of tumor cells while maintaining their viability at large sample sizes, this technology can be used in developing personalized treatments that target the most aggressive cancerous cells. V C 2016 AIP Publishing LLC. [http://dx

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“…2d,e). Previous studies demonstrated that the PC3 cell line retains a small fraction of cells (~1%) that can initiate serially transplantable tumors 32,33 and can be distinguished by their ability to form holoclones, which are small, dense colonies with a high capacity for self-renewal 34,35 . Remarkably, unlike control knockdown cells, PC3 cells stably depleted of BAZ2A were unable to form holoclones and meroclones (an intermediate phenotype of holoclones) and generated only paraclones, which retain no self-renewal capacity ( Fig.…”

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confidence: 99%

BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence

et al. 2014

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Prostate cancer is driven by a combination of genetic and/or epigenetic alterations. Epigenetic alterations are frequently observed in all human cancers, yet how aberrant epigenetic signatures are established is poorly understood. Here we show that the gene encoding BAZ2A (TIP5), a factor previously implicated in epigenetic rRNA gene silencing, is overexpressed in prostate cancer and is paradoxically involved in maintaining prostate cancer cell growth, a feature specific to cancer cells. BAZ2A regulates numerous protein-coding genes and directly interacts with EZH2 to maintain epigenetic silencing at genes repressed in metastasis. BAZ2A overexpression is tightly associated with a molecular subtype displaying a CpG island methylator phenotype (CIMP). Finally, high BAZ2A levels serve as an independent predictor of biochemical recurrence in a cohort of 7,682 individuals with prostate cancer. This work identifies a new aberrant role for the epigenetic regulator BAZ2A, which can also serve as a useful marker for metastatic potential in prostate cancer.

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Aldehyde dehydrogenase activity selects for the holoclone phenotype in prostate cancer cells

Cited by 33 publications

References 30 publications

Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow

Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence

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