scholarly journals Translational models of 3-D organoids and cancer stem cells in gastric cancer research

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kenly Wuputra ◽  
Chia-Chen Ku ◽  
Kohsuke Kato ◽  
Deng-Chyang Wu ◽  
Shigeo Saito ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Genetic Manipulation ◽  
Current Knowledge ◽  
Cancer Microenvironment

AbstractIt is postulated as a general concept of cancer stem cells (CSCs) that they can produce cancer cells overtly and repopulate cancer progenitor cells indefinitely. The CSC niche is part of a specialized cancer microenvironment that is important to keep the phenotypes of CSCs. Stem cell- and induced pluripotent stem cell (iPSC)-derived organoids with genetic manipulation are beneficial to the investigation of the regulation of the microenvironment of CSCs. It would be useful to assess the efficiency of the cancer microenvironment on initiation and progression of cancers. To identify CSCs in cancer tissues, normal cell organoids and gastric cancer organoids from the cancerous areas, as well as iPSCs, were established several years ago. However, many questions remain about the extent to which these cultures recapitulate the development of the gastrointestinal tract and the mechanism of Helicobacter pylori-induced cancer progression. To clarify the fidelity of human organoid models, we have noted several key issues for the cultivation of, and differences between, normal and cancerous organoids. We developed precise culture conditions for gastric organoids in vitro to improve the accuracy of the generation of organoid models for therapeutic and medical applications. In addition, the current knowledge on gastrointestinal CSC research, including the topic of CSC markers, cancer cell reprogramming, and application to target cancer cell plasticity through niches, should be reinforced. We discuss the progression of cancers derived from human gastric organoids and the identification of CSCs.

scholarly journals Gastric Cancer Stem Cells

2008 ◽  
Vol 26 (17) ◽  
pp. 2876-2882 ◽  
Author(s):  
Shigeo Takaishi ◽  
Tomoyuki Okumura ◽  
Timothy C. Wang
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Cell Biology ◽  
Cancer Biology ◽  
Human Cancer ◽  
Immunodeficient Mice

Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony formation in serum-free media in vitro, as well as tumorigenic ability in immunodeficient mice in vivo. We will also discuss the possible origins of the gastric cancer stem cell from an organ-specific stem cell versus a recently recognized new candidate bone marrow–derived cell (BMDC). We have previously shown that BMDC contributed to malignant epithelial cells in the mouse model of Helicobacter-associated gastric cancer. On the basis of these findings from animal model, we propose that a similar phenomenon may also occur in human cancer biology, particularly in the cancer origin of other inflammation-associated cancers. The expanding research field of cancer stem-cell biology may offer a novel clinical apparatus to the diagnosis and treatment of cancer.

scholarly journals LncRNA ASAP1-IT1 enhances cancer cell stemness via regulating miR-509-3p/YAP1 axis in NSCLC

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yantao Liu ◽  
Yuping Yang ◽  
Lingli Zhang ◽  
Jiaqiang Lin ◽  
Bin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Qrt Pcr

Abstract Background Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. Results ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. Conclusions YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

scholarly journals A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 177 ◽  
Author(s):  
Yuki Katsura ◽  
Toshiaki Ohara ◽  
Kazuhiro Noma ◽  
Takayuki Ninomiya ◽  
Hajime Kashima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Iron Metabolism ◽  
Human Cancer ◽  
Iron Chelator ◽  
Novel Therapy ◽  
Human Cancer Cell Lines

Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.

scholarly journals LncRNA ASAP1-IT1 Enhances Cancer Cell Stemness via Regulating miR-509-3p/YAP1 Axis in NSCLC

2021 ◽  
Author(s):  
Yantao Liu ◽  
Yuping Yang ◽  
Lingli Zhang ◽  
Jiaqiang Lin ◽  
Bin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Qrt Pcr

Abstract Background: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is mainly responsible for the poor clinical outcome of NSCLC. Although previous reports indicated long noncoding RNAs (lncRNAs) play important roles in cancer stemness maintain, the underlying causes mechanisms remain is still mysterious. Our study aims to investigate the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods: qRT-PCR analysis the expression of ASAP1-IT1 and microRNA-509-3p (miR-509-3p) in NSCLC tissues, cancer cells and spheres of cancer cells-derived cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection. Sphere formation and colony formation detects NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays analyzed the interaction between lncRNA and miRNA, qRT-PCR and Western blot detect ASAP1-IT1/miR-509-3p axis's regulation on the expression of regulated genes. NSCLC xenograft mice model validates ASAP1-IT1 role in NSCLC stemness and tumor growth in vivo. Results: ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulated ASAP1-IT1 or miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked miR-509-3p mediated regulation of stem cell-like properties, cell growth, and cell apoptosis of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p.Conclusions: YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness，and targeting related signaling is a promising therapeutic strategy to overcome NSCLC stemness.

scholarly journals LncRNA ASAP1-IT1 Enhances Cancer Cell Stemness via Regulating miR-509-3p/YAP1 Axis in NSCLC

2021 ◽  
Author(s):  
Yantao Liu ◽  
Yuping Yang ◽  
Lingli Zhang ◽  
Jiaqiang Lin ◽  
Bin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Qrt Pcr

Abstract Background: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is mainly responsible for the poor clinical outcome of NSCLC. Although previous reports indicated long noncoding RNAs (lncRNAs) play important roles in cancer stemness maintain, the underlying causes mechanisms remain is still mysterious. Our study aims to investigate the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods: qRT-PCR analysis the expression of ASAP1-IT1 and microRNA-509-3p (miR-509-3p) in NSCLC tissues, cancer cells and spheres of cancer cells-derived cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection. Sphere formation and colony formation detects NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays analyzed the interaction between lncRNA and miRNA, qRT-PCR and Western blot detect ASAP1-IT1/miR-509-3p axis's regulation on the expression of regulated genes. NSCLC xenograft mice model validates ASAP1-IT1 role in NSCLC stemness and tumor growth in vivo. Results: ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulated ASAP1-IT1 or miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked miR-509-3p mediated regulation of stem cell-like properties, cell growth, and cell apoptosis of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p.Conclusions: YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness，and targeting related signaling is a promising therapeutic strategy to overcome NSCLC stemness.

scholarly journals Metformin’s Modulatory Effects on miRNAs Function in Cancer Stem Cells—A Systematic Review

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1401
Author(s):  
Bartosz Malinowski ◽  
Nikola Musiała ◽  
Michał Wiciński
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Solid Tumors ◽  
Cancer Progression ◽  
Mechanism Of Action ◽  
Eligibility Criteria ◽  
Major Function ◽  
Mirnas Expression ◽  
Meta Analyses

Cancer stem cells (CSCs) have been reported in various hematopoietic and solid tumors, therefore, are considered to promote cancer progression, metastasis, recurrence and drug resistance. However, regulation of CSCs at the molecular level is not fully understood. microRNAs (miRNAs) have been identified as key regulators of CSCs by modulating their major functions: self-renewal capacity, invasion, migration and proliferation. Various studies suggest that metformin, an anti-diabetic drug, has an anti-tumor activity but its precise mechanism of action has not been understood. The present article was written in accordance to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We systematically reviewed evidence for metformin’s ability to eradicate CSCs through modulating the expression of miRNAs in various solid tumors. PubMed and MEDLINE were searched from January 1990 to January 2020 for in vitro studies. Two authors independently selected and reviewed articles according to predefined eligibility criteria and assessed risk of bias of included studies. Four papers met the inclusion criteria and presented low risk bias. All of the included studies reported a suppression of CSCs’ major function after metformin dosage. Moreover, it was showed that metformin anti-tumor mechanism of action is based on regulation of miRNAs expression. Metformin inhibited cell survival, clonogenicity, wound-healing capacity, sphere formation and promotes chemosensitivity of tumor cells. Due to the small number of publications, aforementioned evidences are limited but may be consider as background for clinical studies.

Colorectal cancer stem cells: Characterization and functional analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4124-4124
Author(s):  
T. Yeung ◽  
J. Wilding ◽  
W. Bodmer
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumour Growth ◽  
Colorectal Cancer Cell Lines ◽  
Colorectal Cancer Stem Cells

4124 Background: Cancer stem cells are defined as cells within a tumour that are able to self-renew and differentiate into all cell lineages within that tumour. With our extensive panel of colorectal cell lines, our aims are: 1) To characterise and isolate cancer stem cells based on stem cell markers, morphological appearances and the ability to form multiple lineages; 2) To understand how cancer stem cells drive tumour growth and progression. Methods: 1) Fluorescent Activated Cell Sorting (FACS); 2) In vitro soft agar clonogenic and Matrigel differentiation assays; 3) In vivo tumourigenic NOD/SCID mice assay; 4) Confocal immunofluorescence imaging. Results: 1) A subpopulation of cells can differentiate into crypt-like megacolonies, retaining the ability to self-renew and differentiate. SW1222 cell line forms heterogeneous colonies when single cells are plated in Matrigel. Megacolonies can both self-renew and form terminally differentiated small colonies, whereas small colonies cannot form megacolonies. Megacolonies develop crypt-like structures and increase their expression of differentiation markers (CDX-1, CK-20) over time. Experiments are currently under way to confirm that cells from megacolonies are able to initiate tumours in NOD/SCID mice. Some cell lines retain the ability to differentiate into both neuroendocrine and epithelial lineages. 2) CD44+CD24+ enriches for the cancer stem cell population. Colorectal cancer cell lines HCT116, HT29, LS180, LS174T and SW1222 express both CD44 and CD24. The CD44+CD24+ subpopulation is the most clonogenic. In SW1222, CD44+CD24+ cells enrich for megacolonies and can reform all four CD44/CD24 subpopulations. 3) Hypoxia reduces differentiation, increases stem-like phenotype and enhances clonogenicity. Hypoxia increases the proportion of undifferentiated colorectal cancer cells when plated on Matrigel and increases clonogenicity. Conclusions: 1) Colorectal cancer cell lines contain subpopulations of cells that have the ability to self-renew, differentiate and drive tumour growth, and may be characterised by their cell surface markers and colony morphology. 2) CD44+CD24+ can be used as markers for colorectal cancer stem cells. 3) Hypoxia increases the stem-like phenotype of cancer cells, reduces differentiation and increases clonogenicity. No significant financial relationships to disclose.

Stem Cells from Human Exfoliated Deciduous Teeth: A Growing Literature

2016 ◽  
Vol 202 (5-6) ◽  
pp. 269-280 ◽  
Author(s):  
Daniel Martinez Saez ◽  
Robson Tetsuo Sasaki ◽  
Adriana da Costa Neves ◽  
Marcelo Cavenaghi Pereira da Silva
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Deciduous Teeth ◽  
Easy Access ◽  
Stem Cell Population ◽  
Scientific Publications ◽  
Human Exfoliated Deciduous Teeth

Adult stem cells research has been considered the most advanced sort of medical-scientific research, particularly stem cells from human exfoliated deciduous teeth (SHED), which represent an immature stem cell population. The purpose of this review is to describe the current knowledge concerning SHED from full-text scientific publications from 2003 to 2015, available in English language and based on the keyword and/or abbreviations ‘stem cells from human exfoliated deciduous teeth (SHED)', and individually presented as to the properties of SHED, immunomodulatory properties of SHED and stem cell banking. In summary, these cell populations are easily accessible by noninvasive procedures and can be isolated, cultured and expanded in vitro, successfully differentiated in vitro and in vivo into odontoblasts, osteoblasts, chondrocytes, adipocytes and neural cells, and present low immune reactions or rejection following SHED transplantation. Furthermore, SHED are able to remain undifferentiated and stable after long-term cryopreservation. In conclusion, the high proliferative capacity, easy access, multilineage differentiation capacity, noninvasiveness and few ethical concerns make stem cells from human exfoliated deciduous teeth the most valuable source of stem cells for tissue engineering and cell-based regenerative medicine therapies.

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