Rejuvenation in distinct cell populations – What does it mean?

Hass, Ralf

doi:10.1016/j.exger.2009.07.006

Cited by 21 publications

(18 citation statements)

References 36 publications

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“…On the other hand, we determined that adipocyte differentiation in the mMSC appeared to be an irreversible process (data not shown). It seemed that prostate cancer stem cells harbored extraordinary mechanisms empowering retrodifferentiation, which is an ancient mechanism invoking apoptosis escape and cell cycle re-entry (37). Considered as an approach to cellular rejuvenation and regeneration, retrodifferentiation has been explored as a treatment for degenerative and dystrophic diseases, but the underlying regulatory mechanism remains obscure.…”

Section: Discussionmentioning

confidence: 99%

Human Prostate Cancer Harbors the Stem Cell Properties of Bone Marrow Mesenchymal Stem Cells

Zhau

Wang

et al. 2011

Clinical Cancer Research

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Purpose Prostate tumor cells frequently show the features of osteoblasts, which are differentiated from bone marrow mesenchymal stem cells. We examined human prostate cancer cell lines and clinical prostate cancer specimens for additional bone marrow mesenchymal stem cell properties. Experimental Design Prostate cancer cell lines were induced for osteoblastogenic and adipogenic differentiation, detected by standard staining methods and confirmed by lineage-specific marker expression. Abnormal expression of the markers was then assessed in clinical prostate cancer specimens. Results After osteoblastogenic induction, cells of the LNCaP lineage, PC-3 lineage and DU145 displayed osteoblastic features. Upon adipogenic induction, PC-3 lineage and DU145 cells differentiated into adipocyte-like cells. The adipocyte-like cancer cells expressed brown adipocyte-specific markers, suggesting differentiation along the brown adipocyte lineage. The adipogenic differentiation was accompanied by growth inhibition, and most of the adipocyte-like cancer cells were committed to apoptotic death. During cyclic treatments with adipogenic differentiation medium and then with control medium, the cancer cells could commit to repeated adipogenic differentiation and retrodifferentiation. In clinical prostate cancer specimens, the expression of UCP1, a brown fat-specific marker, was enhanced with the level of expression correlated to disease progression from primary to bone metastatic cancers. Conclusions This study thus revealed that prostate cancer cells harbor the stem cell properties of bone marrow mesenchymal stem cells. The abnormally expressed adipogenic UCP1 protein may serve as a unique marker, while adipogenic induction can be explored as a differentiation therapy for prostate cancer progression and bone metastasis.

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Section: Discussionmentioning

confidence: 99%

Human Prostate Cancer Harbors the Stem Cell Properties of Bone Marrow Mesenchymal Stem Cells

Zhau

Wang

et al. 2011

Clinical Cancer Research

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“…Phorbol ester treatment of non-adherent human myeloid leukemia cells is associated with cell attachment to form 3-dimensional cell aggregates, growth arrest and monocytic differentiation, and conversely, the reversible process of retrodifferentiation and rejuvenation reveals the loss of previously acquired monocytic features, a regained proliferative capacity and cell detachment to form again a single cell suspension of monoblastoid precursor cells [3,15]. Whereas these findings suggested a tight regulatory relationship between adherence, cell growth and metabolic changes, previous work has documented a predominant role of the β 2 integrin CD11b in TPA-induced adherence of human leukemic cells [5].…”

Section: Discussionmentioning

confidence: 99%

Abolished adherence alters signaling pathways in phorbol ester-induced human U937 cells

et al. 2011

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Phorbol ester (TPA) treatment of human U937 myeloid leukemia cells is associated with increasing adherence and monocyte-like maturation whereby the role of β2 integrin-mediated attachment for subsequent growth properties and the differentiation program remains unclear. Here, stably-transfected U937 cells with a pMTH1 vector containing the β2 integrin gene of CD11b in antisense orientation (asCD11b-U937) demonstrated a significantly reduced proliferative capacity in contrast to control vector transfectants (pMTH1-U937) or wild-type U937 cells. Phorbol ester exposure induced adherence and growth arrest in more than 90% of pMTH1-U937 and wild-type U937 cells after 72 h. In contrast, TPA-treated asCD11b-U937 failed to attach and the proliferation continued in more than 30% of the cells. Moreover, increased apoptosis appeared in asCD11b-U937 after TPA induction in contrast to pMTH1-U937 cells. In addition, non-specific inhibition of adherence on an agarose surface demonstrated internucleosomal DNA fragmentation in both, pMTH1-U937 and asCD11b-U937 after TPA treatment indicating a functional relationship between abolished adherence, regulation of proliferation and induction of apoptosis. Western blot analysis revealed differences in the expression levels and altered phosphorylation patterns of Pyk-2, pp60src and p42/p44 MAP kinases between pMTH1-U937 and asCD11b-U937 following TPA exposure which was also substantiated by Pyk-2 immunoprecipitation. These findings suggested that induced adherence predominantly mediated by a functional CD11b/CD18 integrin in U937 cells is involved in the activation of downstream signaling kinases and contributes to cell cycle regulation and apoptosis during monocytic maturation.

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“…Thus, miR which target distinct DNA-methyl transferases can promote senescence of MSC [133]. Although the molecular mechanisms of MSC senescence after a limited number of cell divisions are still poorly understood, cell fusion processes which are known for MSC or asymmetric cell divisions may also contribute to this phenomenon which enables the segregation of daughter cells committed to either senescence or retaining reproductive capacity in correspondence to the parental cells [134]. …”

Section: Effects Of Micro Rna In Mscmentioning

confidence: 99%

Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC

et al. 2011

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The mesenchymal stroma harbors an important population of cells that possess stem cell-like characteristics including self renewal and differentiation capacities and can be derived from a variety of different sources. These multipotent mesenchymal stem cells (MSC) can be found in nearly all tissues and are mostly located in perivascular niches. MSC have migratory abilities and can secrete protective factors and act as a primary matrix for tissue regeneration during inflammation, tissue injuries and certain cancers.These functions underlie the important physiological roles of MSC and underscore a significant potential for the clinical use of distinct populations from the various tissues. MSC derived from different adult (adipose tissue, peripheral blood, bone marrow) and neonatal tissues (particular parts of the placenta and umbilical cord) are therefore compared in this mini-review with respect to their cell biological properties, surface marker expression and proliferative capacities. In addition, several MSC functions including in vitro and in vivo differentiation capacities within a variety of lineages and immune-modulatory properties are highlighted. Differences in the extracellular milieu such as the presence of interacting neighbouring cell populations, exposure to proteases or a hypoxic microenvironment contribute to functional developments within MSC populations originating from different tissues, and intracellular conditions such as the expression levels of certain micro RNAs can additionally balance MSC function and fate.

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Rejuvenation in distinct cell populations – What does it mean?

Cited by 21 publications

References 36 publications

Human Prostate Cancer Harbors the Stem Cell Properties of Bone Marrow Mesenchymal Stem Cells

Human Prostate Cancer Harbors the Stem Cell Properties of Bone Marrow Mesenchymal Stem Cells

Abolished adherence alters signaling pathways in phorbol ester-induced human U937 cells

Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC

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