scholarly journals GABA’s Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches

Physiology ◽  
2009 ◽  
Vol 24 (3) ◽  
pp. 171-185 ◽  
Author(s):  
Stephanie Z. Young ◽  
Angélique Bordey
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Nervous System ◽  
Tumor Cells ◽  
Adult Stem Cells ◽  
Cancer Cell Proliferation ◽  
Tumor Stem Cells ◽  
Adult Tissue ◽  
Amino Butyric Acid ◽  
Regulation Of Secretion

Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery that controls the proliferation of tumor cells and perhaps tumor stem cells. Here, we will discuss GABA’s presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity.

scholarly journals Dual Inhibition of Activin/Nodal/TGF-βand BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Vedavathi Madhu ◽  
Abhijit S. Dighe ◽  
Quanjun Cui ◽  
D. Nicole Deal
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neuronal Differentiation ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Bmp Signaling ◽  
Specific Marker ◽  
Adipose Derived Stem Cells ◽  
Neuronal Marker ◽  
Dual Inhibition

Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-βand BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs) as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally,in vitrosubcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair.

scholarly journals The Effects of TGF-β Signaling on Cancer Cells and Cancer Stem Cells in the Bone Microenvironment

2019 ◽  
Vol 20 (20) ◽  
pp. 5117 ◽  
Author(s):  
Mitsuru Futakuchi ◽  
Kris Lami ◽  
Yuri Tachibana ◽  
Yukari Yamamoto ◽  
Masahiro Furukawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Skin Flap ◽  
Chemotherapeutic Agents ◽  
Bmp Signaling ◽  
Bone Microenvironment

Background: Transforming growth factor-β (TGF-β) plays a key role in bone metastasis formation; we hypothesized the possible involvement of TGF-β in the induction of cancer stem cells (CSCs) in the bone microenvironment (micro-E), which may be responsible for chemo-resistance. Methods: Mouse mammary tumor cells were implanted under the dorsal skin flap over the calvaria and into a subcutaneous (subQ) lesions in female mice, generating tumors in the bone and subQ micro-Es. After implantation of the tumor cells, mice were treated with a TGF-β R1 kinase inhibitor (R1-Ki). Results: Treatment with R1-Ki decreased tumor volume and cell proliferation in the bone micro-E, but not in the subQ micro-E. R1-Ki treatment did not affect the induction of necrosis or apoptosis in either bone or subQ micro-E. The number of cells positive for the CSC markers, SOX2, and CD166 in the bone micro-E, were significantly higher than those in the subQ micro-E. R1-Ki treatment significantly decreased the number of CSC marker positive cells in the bone micro-E but not in the subQ micro-E. TGF-β activation of the MAPK/ERK and AKT pathways was the underlying mechanism of cell proliferation in the bone micro-E. BMP signaling did not play a role in cell proliferation in either micro-E. Conclusion: Our results indicated that the bone micro-E is a key niche for CSC generation, and TGF-β signaling has important roles in generating CSCs and tumor cell proliferation in the bone micro-E. Therefore, it is critically important to evaluate responses to chemotherapeutic agents on both cancer stem cells and proliferating tumor cells in different tumor microenvironments in vivo.

MicroRNA-134 inhibits tumor stem cell migration and invasion in oral squamous cell carcinomas via downregulation of PI3K-Akt signaling pathway by inhibiting LAMC2 expression

2020 ◽  
Vol 29 (1) ◽  
pp. 51-67 ◽  
Author(s):  
Yong-Mei Zhou ◽  
Yi-Lin Yao ◽  
Wei Liu ◽  
Xue-Min Shen ◽  
Lin-Jun Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Nude Mice ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Tumor Stem Cells ◽  
Akt Signaling Pathway

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the mouth. Some studies have found that multiple microRNAs (miRs) participate in OSCC physiological and pathological processes. METHODS: We explored the mechanism of action of miR-134 in OSCC involving the PI3K-Akt signaling pathway. Different bioinformatics methods were used to analyze the potential genes and their related miRs in OSCC. Tumor stem cells were separated from OSCCs through magnetic cell sorting. Regulatory pattern between miR-134 and LAMC2 in OSCC was evaluated by ectopic expression, knockdown and reporter assay experiments. The expression of miR-134, LAMC2, genes in PI3K-Akt signaling pathway, and apoptosis-related genes was detected. Cell proliferation was assessed by MTT assay, cell invasion by scratch test, cell migration by Transwell assay, cell cycle and apoptosis by flow cytometry, and cell growth and migration by xenograft tumor in nude mice. LAMC2 was predicted as the crucial factor related to OSCC using different chip data, and miR-134 was predicted to specifically bind LAMC2 in all five databases. RESULTS: Overexpressed miR-134 or silenced LAMC2 was observed to inhibit cell proliferation, migration, invasion of OSCC cells, growth of subcutaneous xenograft in nude mice, as well as promote OSCC cell apoptosis. LAMC2, a target gene of miR-134, decreased following miR-134 promotion, while the PI3K-Akt signaling pathway was inactivated following LAMC2 knockdown. Furthermore, we also observed that the effect of overexpressed miR-134 was enhanced when LAMC2 was knocked down. CONCLUSIONS: Taken together, these findings suggest that miR-134-mediated direct downregulation of LAMC2 inhibits migration and invasion of tumor stem cells in OSCC by suppressing the PI3K-Akt signaling pathway.

scholarly journals Application of Nanoscaffolds in Mesenchymal Stem Cell-Based Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Saman Ghoraishizadeh ◽  
Afsoon Ghorishizadeh ◽  
Peyman Ghoraishizadeh ◽  
Nasibeh Daneshvar ◽  
Mohadese Hashem Boroojerdi
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Regenerative Medicine ◽  
Adult Stem Cells ◽  
Cell Signalling ◽  
Great Influence ◽  
Source Characterization ◽  
Differentiation Potential ◽  
Cell Based Therapy ◽  
Essential Components

Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling which has a great influence on cell proliferation, differentiation, and biology. Recently, application of scaffolds and MSCs is being utilized in obtaining more homogenous population of MSCs with higher cell proliferation rate and greater differentiation potential, which are crucial factors in regenerative medicine. In this review, the definition, biology, source, characterization, and isolation of MSCs and current report of application of nanofibers in regenerative medicine in different lesions are discussed.

scholarly journals Antiproliferative Effect of Mesenchymal Stem Cells on Human Breast Carcinoma: New Insight on FOXO/lncRNA-AF085935 Axis

2021 ◽  
Vol 9 (A) ◽  
pp. 748-752
Author(s):  
Sahar Hassan Ahmed ◽  
Abeer Mostafa ◽  
Amany Abou-Elalla
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Breast Carcinoma ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Cancer Proliferation ◽  
Cancer Breast ◽  
Anti Inflammatory

AIM: Cancer breast is one of the most common cancer in women leading to death; that is why we are in urgent need to develop new modalities of treatment. Mesenchymal stem cells (MSCs) have an anti-inflammatory effect due to capability to regenerate the damaged tissues. METHODS: MCF7 breast cancer cells were divided into two groups; group 1: untreated cancer cells, group 2: cancer cell cocultured with MSCs; after 24 incubation the cells from the two groups were collected to assess cell proliferation, Interleukin-6 (IL-6) levels and genes expression of Nuclear factor-kappa B (NF-KB), FOXO, and LncRNA AF085935. RESULTS: Statistically significant decrease in cancer cell proliferation and all other studied parameters in cancer cells after coculture with MSCs. CONCLUSION: Breast carcinoma once initiated; it runs in a vicious circle due to stimulation of FOXO/LncRNA AF085935 axis by the inflammatory mediators released from cancer environment. FOXO/LncRNA AF085935 induces cancer proliferation and survival; furthermore, FOXO once induced, it produces further induction of inflammatory cytokines IL-6 and NF-KB and so on, MSCs due to its anti-inflammatory role could break this circle and thus inhibit cancer cell proliferation.

scholarly journals A Novel Fluorescent Dye Invades Mitochondria to Selectively Kill Cancer Stem Cells via Increased ROS Production

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bei-Bei Zhang ◽  
Jun-gang Liu ◽  
Xian-Yu Bai ◽  
Yuan-Jiao Huang ◽  
Ning Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Diagnosis ◽  
Drug Exposure ◽  
Fluorescent Dye ◽  
Cancer Cell Proliferation ◽  
Ros Production

Development of multiple agents has a significant impact on the cancer diagnosis and therapy. Several fluorescent dyes including near-infrared (NIR) fluorescent agents have been already well studied in the field of photodynamic therapy (PDT). In the present study, we reported a novel fluorescent dye could obviously inhibit cancer cell proliferation with slight toxic effects on the biological organism. Furthermore, it displayed selective staining on cancer cells, particularly on cancer stem cells (CSCs), rather than normal cells. Mechanically, this dye preferred to invading mitochondria of cancer cells and inducing overwhelming reactive oxygen species (ROS) production. The in vivo experiments further demonstrated that this dye could image cancer cells and even CSCs in a short-time intratumor injection manner using a zebrafish model and subsequently inhibit cancer cell proliferation after a relatively long-time drug exposure. Taken together, the future development of this agent will promise to make an essential contribution to the cancer diagnosis and therapeutics.

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