scholarly journals The glycoprotein GP130 governs the surface presentation of the G protein–coupled receptor APLNR

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Kilian Trillet ◽  
Kathryn A. Jacobs ◽  
Gwennan André-Grégoire ◽  
An Thys ◽  
Clément Maghe ◽  
...  
Keyword(s):  
Stem Cells ◽  
G Protein ◽  
Ex Vivo ◽  
Tumor Formation ◽  
Brain Endothelial Cells ◽  
Self Renewal ◽  
Vascular Bed ◽  
Signaling Axis ◽  
G Protein Coupled

Glioblastoma is one of the most lethal forms of adult cancer, with a median survival of ∼15 mo. Targeting glioblastoma stem-like cells (GSCs) at the origin of tumor formation and relapse may prove beneficial. In situ, GSCs are nested within the vascular bed in tight interaction with brain endothelial cells, which positively control their expansion. Because GSCs are notably addicted to apelin (APLN), sourced from the surrounding endothelial stroma, the APLN/APLNR nexus has emerged as a druggable network. However, how this signaling axis operates in gliomagenesis remains underestimated. Here, we find that the glycoprotein GP130 interacts with APLNR at the plasma membrane of GSCs and arbitrates its availability at the surface via ELMOD1, which may further impact on ARF-mediated endovesicular trafficking. From a functional standpoint, interfering with GP130 thwarts APLNR-mediated self-renewal of GSCs ex vivo. Thus, GP130 emerges as an unexpected cicerone to the G protein–coupled APLN receptor, opening new therapeutic perspectives toward the targeting of cancer stem cells.

scholarly journals Propofol Inhibits the Proliferation, Migration, and Stem-like Properties of Bladder Cancer Mainly by Suppressing the Hedgehog Pathway

2021 ◽  
Vol 30 ◽  
pp. 096368972098511
Author(s):  
Gang Li ◽  
Xu Zhang ◽  
Xiangyang Guo ◽  
Yi Li ◽  
Chong Li
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Bladder Tumor ◽  
Therapeutic Agent ◽  
Tumor Formation ◽  
The Self ◽  
Hedgehog Pathway ◽  
Self Renewal ◽  
Intravenous Anesthetic ◽  
Novel Therapeutic

Bladder cancer is one of the most common malignancies. The existence of bladder cancer stem cells (BCSCs) has been suggested to underlie bladder tumor initiation and recurrence. Propofol is a commonly used intravenous anesthetic. Here, we find that propofol can dramatically block the activation of Hedgehog pathway in BCSCs. The propofol strongly repressed the growth of cancer cells. Attenuated proliferation and enhanced apoptosis of tumor cells were observed upon propofol stimulation. Furthermore, propofol reduced the self-renewal ability of BCSCs as well as the tumor formation. In conclusion, propofol is potentially used as a novel therapeutic agent for bladder cancer by targeting self-renewal through inhibiting Hedgehog pathway.

scholarly journals Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic loci in orthotopic neuroblastoma model

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiao-Le Yu ◽  
Shing Chan ◽  
Marcus Kwong-Lam Fung ◽  
Godfrey Chi-Fung Chan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Primary Tumor ◽  
Imaging System ◽  
Ex Vivo ◽  
Tumor Formation ◽  
Human Neuroblastoma Cell ◽  
Fluorescence Signal ◽  
Human Neuroblastoma

Abstract Background Majority of neuroblastoma patients develop metastatic disease at diagnosis and their prognosis is poor with current therapeutic approach. Major challenges are how to tackle the mechanisms responsible for tumorigenesis and metastasis. Human mesenchymal stem cells (hMSCs) may be actively involved in the constitution of cancer microenvironment. Methods An orthotopic neuroblastoma murine model was utilized to mimic the clinical scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without hMSCs into the adrenal area of SCID-beige mice. The growth and metastasis of neuroblastoma was observed by using Xenogen IVIS 100 in vivo imaging and evaluating gross tumors ex vivo. The homing of hMSCs towards tumor was analyzed by tracing fluorescence signal tagged on hMSCs using CRI Maestro™ imaging system. Results hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and apparently enhanced metastasis of neuroblastoma in vivo. hMSCs could be recruited by primary tumor and also become part of the tumor microenvironment in the metastatic lesion. The metastatic potential was consistently reduced in lung and tumor when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was one of the prime movers in the metastatic process. Conclusions hMSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of hMSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered hMSCs as vehicles for targeted anti-cancer therapy.

scholarly journals Chemogenetic Tools for Causal Cellular and Neuronal Biology

2018 ◽  
Vol 98 (1) ◽  
pp. 391-418 ◽  
Author(s):  
Deniz Atasoy ◽  
Scott M. Sternson
Keyword(s):  
G Protein ◽  
Ex Vivo ◽  
Cell Types ◽  
Cell Populations ◽  
Specific Cell ◽  
Cellular Processes ◽  
Distinct Cell ◽  
G Protein Coupled ◽  
Pharmacological Control

Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo.

scholarly journals G Protein-Coupled Receptor GPR87 Promotes the Expansion of PDA Stem Cells through Activating JAK2/STAT3

2020 ◽  
Vol 17 ◽  
pp. 384-393 ◽  
Author(s):  
Jianxin Jiang ◽  
Chao Yu ◽  
Xingjun Guo ◽  
Hao Zhang ◽  
She Tian ◽  
...  
Keyword(s):  
Stem Cells ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Vascular Abnormalities in Mice Deficient for the G Protein-Coupled Receptor GPR4 That Functions as a pH Sensor

2006 ◽  
Vol 27 (4) ◽  
pp. 1334-1347 ◽  
Author(s):  
Li V. Yang ◽  
Caius G. Radu ◽  
Meenakshi Roy ◽  
Sunyoung Lee ◽  
Jami McLaughlin ◽  
...  
Keyword(s):  
G Protein ◽  
Mesangial Cells ◽  
Ex Vivo ◽  
Extracellular Ph ◽  
Ph Sensing ◽  
G Protein Coupled Receptor ◽  
Vascular Abnormalities ◽  
G Protein Coupled

ABSTRACT GPR4 is a G protein-coupled receptor expressed in the vasculature, lung, kidney, and other tissues. In vitro ectopic overexpression studies implicated GPR4 in sensing extracellular pH changes leading to cyclic AMP (cAMP) production. To investigate its biological roles in vivo, we generated GPR4-deficient mice by homologous recombination. Whereas GPR4-null adult mice appeared phenotypically normal, neonates showed a higher frequency of perinatal mortality. The average litter size from GPR4−/− intercrosses was ∼30% smaller than that from GPR4+/+ intercrosses on N3 and N5 C57BL/6 genetic backgrounds. A fraction of knockout embryos and neonates had spontaneous hemorrhages, dilated and tortuous subcutaneous blood vessels, and defective vascular smooth muscle cell coverage. Mesangial cells in kidney glomeruli were also significantly reduced in GPR4-null neonates. Some neonates exhibited respiratory distress with airway lining cell metaplasia. To examine whether GPR4 is functionally involved in vascular pH sensing, an ex vivo aortic ring assay was used under defined pH conditions. Compared to wild-type aortas, microvessel outgrowth from GPR4-null aortas was less inhibited by acidic extracellular pH. Treatment with an analog of cAMP, a downstream effector of GPR4, abolished microvessel outgrowth bypassing the GPR4-knockout phenotype. These results suggest that GPR4 deficiency leads to partially penetrant vascular abnormalities during development and that this receptor functions in blood vessel pH sensing.

Lack of Self-Renewal Capacity in Fancc −/− Stem Cells After Ex Vivo Expansion

Stem Cells ◽  
2005 ◽  
Vol 23 (8) ◽  
pp. 1135-1141 ◽  
Author(s):  
Ouassila Habi ◽  
Marie-Chantal Delisle ◽  
Nancy Messier ◽  
Madeleine Carreau
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Self Renewal
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