scholarly journals Stemness-Attenuating miR-503-3p as a Paracrine Factor to Regulate Growth of Cancer Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Minkoo Seo ◽  
Seung Min Kim ◽  
Eun Young Woo ◽  
Ki-Cheol Han ◽  
Eun Joo Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Cellular Heterogeneity ◽  
Paracrine Factor ◽  
Adipose Stem Cell ◽  
Self Renewal ◽  
Human Adipose Stem Cell ◽  
Pluripotency Genes

Cancer stem cells (CSCs) with self-renewal abilities endorse cellular heterogeneity, resulting in metastasis and recurrence. However, there are no promising therapeutics directed against CSCs. Herein, we found that miR-503-3p inhibited tumor growth via the regulation of CSC proliferation and self-renewal. miR-503-3p, isolated from human adipose stem cell- (ASC-) derived exosomes, suppressed initiation and progression of CSCs as determined by anchorage-dependent (colony formation) and anchorage-independent (tumorsphere formation) assays. The expression of pluripotency genes was significantly decreased in miR-503-3p-treated CSCs. Furthermore, xenografts, which received miR-503-3p, exhibited remarkably reduced tumor growth in vivo. Thus, miR-503-3p may function as a stemness-attenuating factor via cell-to-cell communications.

Unexplored functions of sex hormones in glioblastoma cancer stem cells

Endocrinology ◽  
2022 ◽  
Author(s):  
Juyeun Lee ◽  
Katie Troike ◽  
R’ay Fodor ◽  
Justin D Lathia
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Sex Differences ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Sex Hormones ◽  
Cellular Heterogeneity ◽  
Cellular Functions ◽  
Biological Sex ◽  
Organismal Development

Abstract Biological sex impacts a wide array of molecular and cellular functions that impact organismal development and can influence disease trajectory in a variety of pathophysiological states. In non-reproductive cancers, epidemiological sex differences have been observed in a series of tumors, and recent work has identified previously unappreciated sex differences in molecular genetics and immune response. However, the extent of these sex differences in terms of drivers of tumor growth and therapeutic response is less clear. In glioblastoma, the most common primary malignant brain tumor, there is a male bias in incidence and outcome, and key genetic and epigenetic differences, as well as differences in immune response driven by immune-suppressive myeloid populations, have recently been revealed. Glioblastoma is a prototypic tumor in which cellular heterogeneity is driven by populations of therapeutically resistant cancer stem cells (CSCs) that underlie tumor growth and recurrence. There is emerging evidence that GBM CSCs may show a sex difference, with male tumor cells showing enhanced self-renewal, but how sex differences impact CSC function is not clear. In this mini-review, we focus on how sex hormones may impact CSCs in GBM and implications for other cancers with a pronounced CSC population. We also explore opportunities to leverage new models to better understand the contribution of sex hormones versus sex chromosomes to CSC function. With the rising interest in sex differences in cancer, there is an immediate need to understand the extent to which sex differences impact tumor growth, including effects on CSC function.

scholarly journals ID: 1023 All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth

2017 ◽  
Vol 4 (S) ◽  
pp. 98
Author(s):  
P H Nguyen ◽  
J Giraud ◽  
C Staedel ◽  
L Chambonnier ◽  
P Dubus ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Gastric Carcinoma ◽  
Tumor Growth ◽  
Cell Cycle Progression ◽  
3D Culture ◽  
All Trans Retinoic Acid

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy. In this study, we evaluated the effects of all-transretinoic acid (ATRA) on CSCs in human gastric carcinoma. ATRA effects were evaluated on the proliferation and tumorigenic properties of gastric carcinoma cells from patient-derived tumors and cell lines in conventional 2D cultures, in 3D culture systems (tumorsphere assay) and in mouse xenograft models. ATRA inhibited both tumorspheres initiation and growth in vitro, which was associated with a cell-cycle arrest through the upregulation of cyclin-dependent kinase (CDK) inhibitors and the downregulation of cell-cycle progression activators. More importantly, ATRA downregulated the expression of the CSC markers CD44 and ALDH as well as stemness genes such as Klf4 and Sox2 and induced differentiation of tumorspheres. Finally, 2 weeks of daily ATRA treatment were sufficient to inhibit gastric tumor progression in vivo, which was associated with a decrease in CD44, ALDH1, Ki67 and PCNA expression in the remaining tumor cells. Administration of ATRA appears to be a potent strategy to efficiently inhibit tumor growth and more importantly to target gastric CSCs in both intestinal and diffuse types of gastric carcinoma.

scholarly journals MicroRNA-28-5p Regulates Liver Cancer Stem Cell Expansion via IGF-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Qing Xia ◽  
Tao Han ◽  
Pinghua Yang ◽  
Ruoyu Wang ◽  
Hengyu Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Critical Role ◽  
Self Renewal ◽  
Sorafenib Treatment ◽  
The Impact

Background. MicroRNAs (miRNAs) play a critical role in the regulation of cancer stem cells (CSCs). However, the role of miRNAs in liver CSCs has not been fully elucidated. Methods. Real-time PCR was used to detect the expression of miR-miR-28-5p in liver cancer stem cells (CSCs). The impact of miR-28-5p on liver CSC expansion was investigated both in vivo and in vitro. The correlation between miR-28-5p expression and sorafenib benefits in HCC was further evaluated in patient-derived xenografts (PDXs). Results. Our data showed that miR-28-5p was downregulated in sorted EpCAM- and CD24-positive liver CSCs. Biofunctional investigations revealed that knockdown miR-28-5p promoted liver CSC self-renewal and tumorigenesis. Consistently, miR-28-5p overexpression inhibited liver CSC’s self-renewal and tumorigenesis. Mechanistically, we found that insulin-like growth factor-1 (IGF-1) was a direct target of miR-28-5p in liver CSCs, and the effects of miR-28-5p on liver CSC’s self-renewal and tumorigenesis were dependent on IGF-1. The correlation between miR-28-5p and IGF-1 was confirmed in human HCC tissues. Furthermore, the miR-28-5p knockdown HCC cells were more sensitive to sorafenib treatment. Analysis of patient-derived xenografts (PDXs) further demonstrated that the miR-28-5p may predict sorafenib benefits in HCC patients. Conclusion. Our findings revealed the crucial role of the miR-28-5p in liver CSC expansion and sorafenib response, rendering miR-28-5p an optimal therapeutic target for HCC.

scholarly journals Cancer stem cells enrichment with surface markers CD271 and CD44 in human head and neck squamous cell carcinomas

2019 ◽  
Vol 41 (4) ◽  
pp. 458-466 ◽  
Author(s):  
Osama A Elkashty ◽  
Ghada Abu Elghanam ◽  
Xinyun Su ◽  
Younan Liu ◽  
Peter J Chauvin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Colony Formation ◽  
Self Renewal ◽  
Tissue Samples ◽  
Hnscc Cell

Abstract Head and neck squamous cell carcinoma (HNSCC) has a poor 5-year survival rate of 50%. One potential reason for treatment failure is the presence of cancer stem cells (CSCs). Several cell markers, particularly CD44, have been used to isolate CSCs. However, isolating a pure population of CSC in HNSCC still remains a challenging task. Recent findings show that normal oral stem cells were isolated using CD271 as a marker. Thus, we investigated the combined use of CD271 and CD44 to isolate an enriched subpopulation of CSCs, followed by their characterization in vitro, in vivo, and in patients’ tissue samples. Fluorescent-activated cell sorting was used to isolate CD44+/CD271+ and CD44+/CD271− from two human HNSCC cell lines. Cell growth and self-renewal were measured with MTT and sphere/colony formation assays. Treatment-resistance was tested against chemotherapy (cisplatin and 5-fluorouracil) and ionizing radiation. Self-renewal, resistance, and stemness-related genes expression were measured with qRT-PCR. In vivo tumorigenicity was tested with an orthotopic immunodeficient mouse model of oral cancer. Finally, we examined the co-localization of CD44+/CD271+ in patients’ tissue samples. We found that CD271+ cells were a subpopulation of CD44+ cells in human HNSCC cell lines and tissues. CD44+/CD271+ cells exhibited higher cell proliferation, sphere/colony formation, chemo- and radio-resistance, upregulation of CSCs-related genes, and in vivo tumorigenicity when compared to CD44+/CD271− or the parental cell line. These cell markers showed increased expression in patients with the increase of the tumor stage. In conclusion, using both CD44 and CD271 allowed the isolation of CSCs from HNSCC. These enriched CSCs will be more relevant in future treatment and HNSCC progression studies.

scholarly journals Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Shui Ma ◽  
Xiao-Li Yang ◽  
Yu-Shan Liu ◽  
Hua Ding ◽  
Jian-Jun Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Viability ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Loss Of Function ◽  
Self Renewal

Abstract Background Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. Methods Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. Results LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. Conclusion Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

scholarly journals Estimating stem cell fractions in hierarchically organized tumors

2015 ◽  
Author(s):  
Benjamin Werner ◽  
Jacob G Scott ◽  
Andrea Sottoriva ◽  
Alexander RA Anderson ◽  
Arne Traulsen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Treatment Strategies ◽  
Exact Result ◽  
Growth Patterns ◽  
Cell Fractions ◽  
Tumor Types

Cancers arise as a result of genetic and epigenetic alterations. These accumulate in cells during the processes of tissue development, homeostasis and repair. Many tumor types are hierarchically organized and driven by a sub-population of cells often called cancer stem cells. Cancer stem cells are uniquely capable of recapitulating the tumor and can be highly resistant to radio- and chemotherapy treatment. We investigate tumor growth patterns from a theoretical standpoint and show how significant changes in pre- and post-therapy tumor dynamics are tied to the dynamics of cancer stem cells. We identify two characteristic growth regimes of a tumor population that can be leveraged to estimate cancer stem cell fractions in vivo using simple linear regression. Our method is a mathematically exact result, parameter free and does not require any microscopic knowledge of the tumor properties. A more accurate quantification of the direct link between the sub-population driving tumor growth and treatment response promises new ways to individualize treatment strategies.

scholarly journals Cancer Stem Cells and Macrophages: Implications in Tumor Biology and Therapeutic Strategies

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Bruno Sainz ◽  
Emily Carron ◽  
Mireia Vallespinós ◽  
Heather L. Machado
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cross Talk ◽  
Tumor Biology ◽  
Cell Types ◽  
Tumor Formation ◽  
Self Renewal ◽  
Numerous Cell ◽  
Key Drivers

Cancer stem cells (CSCs) are a unique subset of cells within tumors with stemlike properties that have been proposed to be key drivers of tumor initiation and progression. CSCs are functionally defined by their unlimited self-renewal capacity and their ability to initiate tumor formationin vivo. Like normal stem cells, CSCs exist in a cellular niche comprised of numerous cell types including tumor-associated macrophages (TAMs) which provides a unique microenvironment to protect and promote CSC functions. TAMs provide pivotal signals to promote CSC survival, self-renewal, maintenance, and migratory ability, and in turn, CSCs deliver tumor-promoting cues to TAMs that further enhance tumorigenesis. Studies in the last decade have aimed to understand the molecular mediators of CSCs and TAMs, and recent advances have begun to elucidate the complex cross talk that occurs between these two cell types. In this review, we discuss the molecular interactions that define CSC-TAM cross talk at each stage of tumor progression and examine the clinical implications of targeting these interactions.

scholarly journals Chemosensitization of prostate cancer stem cells in mice by angiogenin and plexin-B2 inhibitors

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Shuping Li ◽  
Kevin A. Goncalves ◽  
Baiqing Lyu ◽  
Liang Yuan ◽  
Guo-fu Hu
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Ribosomal Rna ◽  
Protein Translation ◽  
Chemotherapeutic Agents ◽  
Self Renewal ◽  
5S Ribosomal Rna ◽  
Prostate Cancer Stem Cells

AbstractCancer stem cells (CSCs) are an obstacle in cancer therapy and are a major cause of drug resistance, cancer recurrence, and metastasis. Available treatments, targeting proliferating cancer cells, are not effective in eliminating quiescent CSCs. Identification of CSC regulators will help design therapeutic strategies to sensitize drug-resistant CSCs for chemo-eradication. Here, we show that angiogenin and plexin-B2 regulate the stemness of prostate CSCs, and that inhibitors of angiogenin/plexin-B2 sensitize prostate CSCs to chemotherapy. Prostate CSCs capable of self-renewal, differentiation, and tumor initiation with a single cell inoculation were identified and shown to be regulated by angiogenin/plexin-B2 that promotes quiescence and self-renewal through 5S ribosomal RNA processing and generation of the bioactive 3′-end fragments of 5S ribosomal RNA, which suppress protein translation and restrict cell cycling. Monoclonal antibodies of angiogenin and plexin-B2 decrease the stemness of prostate CSCs and sensitize them to chemotherapeutic agents in vitro and in vivo.

scholarly journals Between Fate Choice and Self-Renewal—Heterogeneity of Adult Neural Crest-Derived Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Anna L. Höving ◽  
Beatrice A. Windmöller ◽  
Cornelius Knabbe ◽  
Barbara Kaltschmidt ◽  
Christian Kaltschmidt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Crest ◽  
Current Knowledge ◽  
Mapk Signaling ◽  
Cellular Heterogeneity ◽  
Self Renewal ◽  
The Impact

Stem cells of the neural crest (NC) vitally participate to embryonic development, but also remain in distinct niches as quiescent neural crest-derived stem cell (NCSC) pools into adulthood. Although NCSC-populations share a high capacity for self-renewal and differentiation resulting in promising preclinical applications within the last two decades, inter- and intrapopulational differences exist in terms of their expression signatures and regenerative capability. Differentiation and self-renewal of stem cells in developmental and regenerative contexts are partially regulated by the niche or culture condition and further influenced by single cell decision processes, making cell-to-cell variation and heterogeneity critical for understanding adult stem cell populations. The present review summarizes current knowledge of the cellular heterogeneity within NCSC-populations located in distinct craniofacial and trunk niches including the nasal cavity, olfactory bulb, oral tissues or skin. We shed light on the impact of intrapopulational heterogeneity on fate specifications and plasticity of NCSCs in their niches in vivo as well as during in vitro culture. We further discuss underlying molecular regulators determining fate specifications of NCSCs, suggesting a regulatory network including NF-κB and NC-related transcription factors like SLUG and SOX9 accompanied by Wnt- and MAPK-signaling to orchestrate NCSC stemness and differentiation. In summary, adult NCSCs show a broad heterogeneity on the level of the donor and the donors’ sex, the cell population and the single stem cell directly impacting their differentiation capability and fate choices in vivo and in vitro. The findings discussed here emphasize heterogeneity of NCSCs as a crucial parameter for understanding their role in tissue homeostasis and regeneration and for improving their applicability in regenerative medicine.

scholarly journals High B3GALT5 expression confers poor clinical outcome and contributes to tumor progression and metastasis in breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Yu-Mei Liao ◽  
Ya-Hui Wang ◽  
Jung-Tung Hung ◽  
Yu-Ju Lin ◽  
Yen-Lin Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Migration ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Early Stage ◽  
Prognostic Significance ◽  
Mesenchymal Transition

Abstract Background Existence of breast cancer stem cells (BCSCs) is implicated in disease relapse, metastasis, and resistance of treatment. β1,3-Galactosyltransferase 5 (B3GALT5) has been shown to be a pro-survival marker for BCSCs. However, little is known about the prognostic significance of B3GALT5 in breast cancer. Methods Paired tissues (tumor part and adjacent non-tumor part) from a cohort of 202 women with breast cancer were used to determine the expression levels of B3GALT5 mRNA by qRT-PCR. Kaplan–Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of relapse-free survival (RFS) and overall survival (OS). Both breast cancer cells and cancer stem cells (BCSCs) were used to see the in vitro effects of knockdown or overexpression of B3GALT5 on cell migration, invasion, and epithelial-to-mesenchymal transition (EMT). A patient-derived xenograft (PDX) model was used to see the in vivo effects of knockdown of B3GALT5 in BCSCs on tumor growth and metastasis. Results Higher expression of B3GALT5 in 202 breast cancer tissues, especially in adjacent non-tumor tissue, correlated with poor clinical outcomes including shorter OS and RFS in all patients, especially those with early stage breast cancer. In vitro studies showed B3GALT5 could enhance cell migration, invasion, mammosphere formation, and EMT. Of note, B3GALT5 upregulated the expression of β-catenin and EMT activator zinc finger E-box binding homeobox 1 (ZEB1) pathway in BCSCs. In vivo studies showed B3GALT5 expression in BCSCs is critical for not only tumor growth but also lymph node and lung metastasis in PDX mice. Conclusion Our results demonstrated the value of B3GALT5 as a prognostic marker of breast cancer, especially among the early stage patients, and its crucial roles in regulating EMT, cell migration, and stemness thereby promoting breast cancer progression.

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