Preliminary study on the relationship among stem cell markers, drug resistance and PI3K signaling pathway in multiple myeloma (MM) cell

Abstract Background Retinal pigment epithelium (RPE) replacement has been proposed as an efficacious treatment for age-related macular degeneration (AMD), which is the primary cause of vision loss in the elderly worldwide. The embryonic stem cell (ESC) microenvironment has been demonstrated to enable mature cells to gain a powerful proliferative ability and even enhance the stem/progenitor phenotype via activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As the PI3K signaling pathway plays a pivotal role in proliferation and homeostasis of RPE, we hypothesize that the stemness and proliferative capability of RPE can be enhanced by the ESC microenvironment via activation of the PI3K signaling pathway. Methods To investigate whether the ESC microenvironment improves the stem cell phenotype and proliferation properties of human RPE (hRPE) cells by regulating the PI3K signaling pathway, primary hRPE cells were cocultured with either ESCs or human corneal epithelial cells (CECs) for 72 h, after which their proliferation, apoptosis, cell cycle progression, and colony formation were assayed to evaluate changes in their biological characteristics. Gene expression was detected by real-time PCR and protein levels were determined by western blotting or immunofluorescence. LY294002, an antagonist of the PI3K signaling pathway, was used to further confirm the mechanism involved. Results In comparison to hRPE cells cultured alone, hRPE cells cocultured with ESCs had an increased proliferative capacity, reduced apoptotic rate, and higher colony-forming efficiency. The expression of the stem cell-associated marker KLF4 and the differentiation marker CRALBP increased and decreased, respectively, in hRPE cells isolated from the ESC coculture. Furthermore, PI3K pathway-related genes were significantly upregulated in hRPE cells after exposure to ESCs. LY294002 reversed the pro-proliferative effect of ESCs on hRPE cells. In contrast, CECs did not share the ability of ESCs to influence the biological behavior and gene expression of hRPE cells. Conclusions Our findings indicate that the ESC microenvironment enhances stemness and proliferation of hRPE cells, partially via activation of the PI3K signaling pathway. This study may have a significant impact and clinical implication on cell therapy in regenerative medicine, specifically for age-related macular degeneration.

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Sequential Changes in Stem Cell Markers in Peripheral Blood and Leukapheresis Samples after Injections of Recombinant Human Granulocyte Colony-stimulating Factor in Patients with Urogenital Malignant Solid Tumors: A Preliminary Study

Japanese Journal of Clinical Oncology ◽

10.1093/oxfordjournals.jjco.a039720 ◽

1994 ◽

Keyword(s):

Stem Cell ◽

Solid Tumors ◽

Peripheral Blood ◽

Stem Cell Markers ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Cell Markers ◽

Preliminary Study ◽

Stimulating Factor

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Embryonic stem cell microenvironment enhances proliferation of human retinal pigment epithelium cells by activating the PI3K signaling pathway

10.21203/rs.3.rs-27573/v2 ◽

2020 ◽

Author(s):

Jiahui Liu ◽

Liu Yang ◽

Xiaoran Wang ◽

Shoubi Wang ◽

Zheqian Huang ◽

...

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Retinal Pigment Epithelium ◽

Embryonic Stem Cell ◽

Signaling Pathway ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Embryonic Stem ◽

Pi3k Signaling ◽

Pi3k Signaling Pathway

Abstract Purpose This study aimed to investigate whether the mouse embryonic stem cell (ESC) microenvironment improves the stem cell phenotype and proliferation properties of human retinal pigment epithelium (hRPE) cells by regulating the PI3K signaling pathway. Methods Primary hRPE cells were cocultured with either ESCs or human corneal epithelial cells (CECs) for 72 hours, after which their proliferation, apoptosis, cell cycle progression, and colony formation were assayed to evaluate changes in their biological characteristics. Gene expression was detected by real-time PCR and protein levels were determined by western blotting or immunofluorescence. LY294002, an antagonist of the PI3K signaling pathway, was used to further confirm the mechanism involved. Results In comparison to hRPE cells cultured alone, hRPE cells cocultured with ESCs had an increased proliferative capacity, reduced apoptotic rate, and higher colony-forming efficiency. The expression of the stem cell-associated marker KLF4 and the differentiation marker CRALBP increased and decreased, respectively, in hRPE cells isolated from the ESC coculture. Furthermore, PI3K pathway-related genes were significantly up-regulated in hRPE cells after exposure to ESCs. LY294002 reversed the pro-proliferative effect of ESCs on hRPE cells. In contrast, CECs did not share the ability of ESCs to influence the biological behavior and gene expression of hRPE cells. Conclusions Our findings indicate that the ESC microenvironment enhances stemness and proliferation of hRPE cells, partially via activation of the PI3K signaling pathway. This study may have a significant impact and clinical implication on cell therapy in regenerative medicine, specifically for age-related macular degeneration.

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The therapeutic efficacy for targeting the PI3K signaling pathway for fighting breast, prostate and multiple myeloma cancer cells

Journal of Cancer and Biomedical Research ◽

10.21608/jcbr.2019.37768 ◽

2019 ◽

Vol 1 (2) ◽

pp. 37-43

Author(s):

Gamal Badr ◽

Badr Badr

Keyword(s):

Multiple Myeloma ◽

Cancer Cells ◽

Signaling Pathway ◽

Therapeutic Efficacy ◽

Pi3k Signaling ◽

Pi3k Signaling Pathway

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Embryonic stem cell microenvironment enhances proliferation of human retinal pigment epithelium cells by activating the PI3K signaling pathway

10.21203/rs.3.rs-27573/v1 ◽

2020 ◽

Author(s):

Jiahui Liu ◽

Liu Yang ◽

Xiaoran Wang ◽

Shoubi Wang ◽

Zheqian Huang ◽

...

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Retinal Pigment Epithelium ◽

Embryonic Stem Cell ◽

Signaling Pathway ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Embryonic Stem ◽

Pi3k Signaling ◽

Pi3k Signaling Pathway

Abstract Purpose. This study aimed to investigate whether the mouse embryonic stem cell (ESC) microenvironment improves the stem cell phenotype and proliferation properties of human retinal pigment epithelium (hRPE) cells by regulating the PI3K signaling pathway. Methods. Primary hRPE cells were cocultured with either ESCs or human corneal epithelial cells (CECs) for 72 hours, after which their proliferation, apoptosis, cell cycle progression, and colony formation were assayed to evaluate changes in their biological characteristics. Gene expression was detected by real-time PCR and protein levels were determined by western blotting or immunofluorescence. LY294002, an antagonist of the PI3K signaling pathway, was used to further confirm the mechanism involved. Results. In comparison to hRPE cells cultured alone, hRPE cells cocultured with ESCs had an increased proliferative capacity, reduced apoptotic rate, and higher colony-forming efficiency. The expression of the stem cell-associated marker KLF4 and the differentiation marker CRALBP increased and decreased, respectively, in hRPE cells isolated from the ESC coculture. Furthermore, PI3K pathway-related genes were significantly up-regulated in hRPE cells after exposure to ESCs. LY294002 reversed the pro-proliferative effect of ESCs on hRPE cells. In contrast, CECs did not share the ability of ESCs to influence the biological behavior and gene expression of hRPE cells. Conclusions. Our findings indicate that the ESC microenvironment enhances stemness and proliferation of hRPE cells, partially via activation of the PI3K signaling pathway. This study may have a significant impact and clinical implication on cell therapy in regenerative medicine, specifically for age-related macular degeneration.

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Blocking the formation of induced multiple myeloma stem-like cells through PI3K/AKT/mTOR pathway.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e19518 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e19518-e19518

Author(s):

Bingshan Liu ◽

Danyang Wang ◽

Yongping Song

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Stem Cell ◽

Disease Free Survival ◽

Mtor Pathway ◽

Good Effect ◽

Stem Cell Markers ◽

Cell Markers ◽

Positive Expression ◽

Rpmi 8226

e19518 Background: Multiple myeloma (MM) is still an incurable disease. There are many different treatment options and most patients in the early treatment will have a good effect, but some patients will relapse due to acquired drug resistance. The purpose of this study is to investigate the existence of MM stem cells and its relationship with drug resistence. Methods: A total of 53 patients were recruited who underwent MM between 2010 and 2012. We analysed the expression of stem cell markers (Nanog, Oct4 and Sox2) and their relationship with clinical characteristics and 3– year disease free survival (DFS) or overall survival (OS). Then we chose MM cell line RPMI 8226 for the study, explored the possible mechanism of chemotherapy tolerance. Results: We found that that expression levels of Nanog, Oct4 and Sox2 were 11.3% (6/53), 17.0% (9/53) and 20.8% (11/53), respectively. Only positive expression of Sox2 had relationship with ISS stage ( p= 0.049). Furthermore, positive expression of Sox2 ( p= 0.039) was significantly associated with poor DFS. And after induced treatments, RPMI 8226 cells changed, including cell morphology, cell cycle, apoptosis, stem cell markers and changes in signal transduction pathways. Inhibiting PI3K/AKT/mTOR pathway can improve sensitivity to chemotherapy and radiotherapy. Conclusions: These findings demonstated stem cells markers had significant meanings in MM patients’ prognosis. There may be stem-like cells in MM, which is insensitivity to radiotherapy or chemotherapy, and blocking PI3K/AKT/mTOR pathway can reverse it.

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Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons

Cells ◽

10.3390/cells9030644 ◽

2020 ◽

Vol 9 (3) ◽

pp. 644 ◽

Cited By ~ 1

Author(s):

Pierfrancesco Pagella ◽

Javier Catón ◽

Christian T. Meisel ◽

Thimios A. Mitsiadis

Keyword(s):

Stem Cell ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Molecular Characteristics ◽

Stem Cell Markers ◽

Cell Potential ◽

Cell Markers ◽

Non Invasive ◽

Stem Cell Potential

Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis is driven by a plethora of factors, among which innervation has been long neglected. Recent findings have shown that innervation directly promotes tumor progression. On this basis, we investigated the molecular characteristics and neurotrophic properties of human ameloblastomas. Our results showed that ameloblastomas express dental epithelial stem cell markers, as well as components of the Notch signaling pathway, indicating persistence of stemness. We demonstrated that ameloblastomas express classical stem cell markers, exhibit stem cell potential, and form spheres. These tumors express also molecules of the Notch signaling pathway, fundamental for stem cells and their fate. Additionally, we showed that ameloblastomas express the neurotrophic factors NGF and BDNF, as well as their receptors TRKA, TRKB, and P75/NGFR, which are responsible for their innervation by trigeminal axons in vivo. In vitro studies using microfluidic devices showed that ameloblastoma cells attract and form connections with these nerves. Innervation of ameloblastomas might play a key role in the onset of this malignancy and might represent a promising target for non-invasive pharmacological interventions.

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Embryonic stem cell microenvironment enhances proliferation of human retinal pigment epithelium cells by activating the PI3K signaling pathway

10.21203/rs.3.rs-27573/v3 ◽

2020 ◽

Author(s):

Jiahui Liu ◽

Liu Yang ◽

Xiaoran Wang ◽

Shoubi Wang ◽

Zheqian Huang ◽

...

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Signaling Pathway ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Embryonic Stem ◽

Age Related Macular Degeneration ◽

Pi3k Signaling ◽

Age Related ◽

Pi3k Signaling Pathway

Abstract Background: Retinal pigment epithelium (RPE) replacement has been proposed as an efficacious treatment for Age-related macular degeneration (AMD), which is the primary causes of vision loss in the elderly worldwide. The embryonic stem cell (ESC) microenvironment has been demonstrated to enable mature cells to gain a powerful proliferative ability and even enhance the stem/progenitor phenotype via activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As the PI3K signaling pathway plays a pivotal role in proliferation and homeostasis of RPE, we hypothesize that the stemness and proliferative capability of RPE can be enhanced by the ESC microenvironment via activation of the PI3K signaling pathway.Methods: To investigate whether the ESC microenvironment improves the stem cell phenotype and proliferation properties of human RPE (hRPE) cells by regulating the PI3K signaling pathway, primary hRPE cells were cocultured with either ESCs or human corneal epithelial cells (CECs) for 72 hours, after which their proliferation, apoptosis, cell cycle progression, and colony formation were assayed to evaluate changes in their biological characteristics. Gene expression was detected by real-time PCR and protein levels were determined by western blotting or immunofluorescence. LY294002, an antagonist of the PI3K signaling pathway, was used to further confirm the mechanism involved.Results: In comparison to hRPE cells cultured alone, hRPE cells cocultured with ESCs had an increased proliferative capacity, reduced apoptotic rate, and higher colony-forming efficiency. The expression of the stem cell-associated marker KLF4 and the differentiation marker CRALBP increased and decreased, respectively, in hRPE cells isolated from the ESC coculture. Furthermore, PI3K pathway-related genes were significantly up-regulated in hRPE cells after exposure to ESCs. LY294002 reversed the pro-proliferative effect of ESCs on hRPE cells. In contrast, CECs did not share the ability of ESCs to influence the biological behavior and gene expression of hRPE cells.Conclusions: Our findings indicate that the ESC microenvironment enhances stemness and proliferation of hRPE cells, partially via activation of the PI3K signaling pathway. This study may have a significant impact and clinical implication on cell therapy in regenerative medicine, specifically for age-related macular degeneration.

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Patient-Derived Colorectal Cancer Organoids Upregulate Revival Stem Cell Marker Genes following Chemotherapeutic Treatment

Journal of Clinical Medicine ◽

10.3390/jcm9010128 ◽

2020 ◽

Vol 9 (1) ◽

pp. 128 ◽

Cited By ~ 8

Author(s):

Engel ◽

Chan ◽

Nickless ◽

Hlavca ◽

Richards ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Drug Resistance ◽

Stem Cell ◽

Cell Population ◽

Stem Cell Marker ◽

Stem Cell Population ◽

Marker Genes ◽

Stem Cell Markers ◽

Cell Markers

Colorectal cancer stem cells have been proposed to drive disease progression, tumour recurrence and chemoresistance. However, studies ablating leucine rich repeat containing G protein-coupled receptor 5 (LGR5)-positive stem cells have shown that they are rapidly replenished in primary tumours. Following injury in normal tissue, LGR5+ stem cells are replaced by a newly defined, transient population of revival stem cells. We investigated whether markers of the revival stem cell population are present in colorectal tumours and how this signature relates to chemoresistance. We examined the expression of different stem cell markers in a cohort of patient-derived colorectal cancer organoids and correlated expression with sensitivity to 5-fluorouracil (5-FU) treatment. Our findings revealed that there was inter-tumour variability in the expression of stem cell markers. Clusterin (CLU), a marker of the revival stem cell population, was significantly enriched following 5-FU treatment and expression correlated with the level of drug resistance. Patient outcome data revealed that CLU expression is associated with both lower patient survival and an increase in disease recurrence. This suggests that CLU is a marker of drug resistance and may identify cells that drive colorectal cancer progression.

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