Interaction of Glia Cells with Glioblastoma and Melanoma Cells under the Influence of Phytocannabinoids

Brain tumor heterogeneity and progression are subject to complex interactions between tumor cells and their microenvironment. Glioblastoma and brain metastasis can contain 30–40% of tumor-associated macrophages, microglia, and astrocytes, affecting migration, proliferation, and apoptosis. Here, we analyzed interactions between glial cells and LN229 glioblastoma or A375 melanoma cells in the context of motility and cell–cell interactions in a 3D model. Furthermore, the effects of phytocannabinoids, cannabidiol (CBD), tetrahydrocannabidiol (THC), or their co-application were analyzed. Co-culture of tumor cells with glial cells had little effect on 3D spheroid formation, while treatment with cannabinoids led to significantly larger spheroids. The addition of astrocytes blocked cannabinoid-induced effects. None of the interventions affected cell death. Furthermore, glial cell-conditioned media led to a significant slowdown in collective, but not single-cell migration speed. Taken together, glial cells in glioblastoma and brain metastasis micromilieu impact the tumor spheroid formation, cell spreading, and motility. Since the size of spheroid remained unaffected in glial cell tumor co-cultures, phytocannabinoids increased the size of spheroids without any effects on migration. This aspect might be of relevance since phytocannabinoids are frequently used in tumor therapy for side effects.

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The Metabolism Symbiosis Between Pancreatic Cancer and Tumor Microenvironment

Frontiers in Oncology ◽

10.3389/fonc.2021.759376 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ying Li ◽

Ju Zhang ◽

Jie Xu ◽

Shanglong Liu

Keyword(s):

Tumor Microenvironment ◽

Tumor Cells ◽

Tumor Therapy ◽

Tumor Development ◽

Metabolic Reprogramming ◽

Metabolic Adaptation ◽

Metabolic Pattern ◽

New Approach ◽

Complex Interactions ◽

Selective Targeting

Complex interactions occur between tumor cells and the tumor microenvironment. Studies have focused on the mechanism of metabolic symbiosis between tumors and the tumor microenvironment. During tumor development, the metabolic pattern undergoes significant changes, and the optimal metabolic mode of the tumor is selected on the basis of its individual environment. Tumor cells can adapt to a specific microenvironment through metabolic adjustment to achieve compatibility. In this study, the effects of tumor glucose metabolism, lipid metabolism, and amino acid metabolism on the tumor microenvironment and related mechanisms were reviewed. Selective targeting of tumor cell metabolic reprogramming is an attractive direction for tumor therapy. Understanding the mechanism of tumor metabolic adaptation and determining the metabolism symbiosis mechanism between tumor cells and the surrounding microenvironment may provide a new approach for treatment, which is of great significance for accelerating the development of targeted tumor metabolic drugs and administering individualized tumor metabolic therapy.

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Study on the Biological Activity of Anti-Tumor Peptide of Tumstatin

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.183-185.1509 ◽

2011 ◽

Vol 183-185 ◽

pp. 1509-1512

Author(s):

Shu Jing Wang ◽

Ning Chen ◽

Zhang Yi ◽

Jia Liu ◽

Bei Bei Xu

Keyword(s):

Electron Microscopy ◽

Biological Activity ◽

Tumor Cells ◽

Tumor Therapy ◽

Base Sequence ◽

Hepatocarcinoma Cell ◽

Transmission Electron ◽

Proliferation And Apoptosis ◽

One Step

Tumstatin anti-tumor peptide of 19peptide can inhibit the proliferation of melanoma cell. To study its effect on the proliferation and apoptosis of different tumor cells and verify its anti-tumor non-specificity, the base sequence of 19peptide was designed and constructed engineering bacteria. The soluble 19peptide was obtained from one step chitin affinity chromatograph. By such experiment as MTT assay, cell growth curve, TUNEL assay，flow cytometry，transmission electron microscopy(TEM), the biological activity of 19peptide was studied. Experiments in vitro identified that obtained 19peptide could inhibit proliferation of hela cell and hepatocarcinoma cell. It also could promote two tumor cells apoptosis. Its anti-tumor effect will lay foundation on its mechanism of action research and clinically tumor therapy in future.

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Sequential detection of mRNA for the chemokine IL-8 and macrophages (F4/80) in human melanoma

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010014141x ◽

1995 ◽

Vol 53 ◽

pp. 1008-1009

Author(s):

C.D. Bucana ◽

R. Sanchez ◽

R. Singh ◽

I.J. Fidler

Keyword(s):

Tumor Cells ◽

Nude Mice ◽

Constitutive Expression ◽

Metastatic Potential ◽

Melanoma Cells ◽

Human Melanoma ◽

Angiogenic Factor ◽

Infiltrating Cells ◽

Immunoperoxidase Assay ◽

Multifunctional Cytokine

The purpose of this study was to demonstrate by ISH the presence of IL-8 mRNA, and by immunohistochemistry (IHC) the presence of the chemokine IL-8 and the distribution of infiltrating macrophages in subcutaneous melanomas in the same tumor. IL-8 is a multifunctional cytokine produced by melanoma cells, activated macrophages and monocytes and it has been shown to be a growth and angiogenic factor for tumor cells. More recently it was shown that constitutive expression of IL-8 correlated directly with metastatic potential of human melanoma cells in nude mice. IL-8 content of a solid tumor as determined by Western blot analysis does not take into account the contribution of macrophages. Previous studies showed that murine tumors contain many infiltrating cells interspersed among tumor cells whereas human tumors growing in nude mice exhibit macrophages at the periphery or between tumor islands. In this study we demonstrate the expression of IL-8 and the distribution of macrophages by immunoperoxidase assay and IL-8 mRNA by ISH.

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Nano Technological Approach for Anti-Tumor Therapy: Opportunities and Challenges

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681210666200213121156 ◽

2020 ◽

Vol 10 ◽

Author(s):

Krishna Champaneria ◽

Prajesh Prajapati

Keyword(s):

Adverse Effects ◽

Tumor Cells ◽

Targeted Delivery ◽

Blood Circulation ◽

Review Paper ◽

Tumor Therapy ◽

Conventional Chemotherapy ◽

Targeting Delivery ◽

Tumor Accumulation ◽

Work Done

Cancer is one of the reason for mortality and its individual and collective impact is substantial. Conventional chemotherapy utilizes drugs that can destroy Tumor cells effectively. But these agents destroy healthy cells along with the tumor cells, leading to many adverse effects which include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. To minimize the adverse effects, various drug delivery systems (DDSs) has been developed. Among them, nanoparticles are attractive platforms for it. So this review paper explores the recent work done on targeted delivery, enhancing tumor accumulation and longer blood circulation using more effective biomaterial that will enhance the properties of nanoparticles. Moreover, various target-specific delivery of drugs like antibody-targeted, targeting delivery through angiogenesis, mitochondria, CD44 receptor are also explained.

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The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

BMC Cancer ◽

10.1186/s12885-021-08385-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Satu Salmi ◽

Anton Lin ◽

Benjamin Hirschovits-Gerz ◽

Mari Valkonen ◽

Niina Aaltonen ◽

...

Keyword(s):

T Cells ◽

Prognostic Factors ◽

Regulatory T Cells ◽

Tumor Cells ◽

Immune Cells ◽

Positive Association ◽

Tumor Stage ◽

Melanoma Cells ◽

Melanoma Progression

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.

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Three-dimensional relationships between tumor cells and microcirculation with double cyanine immunolabeling, laser scanning confocal microscopy, and computer-assisted reconstruction: an alternative to cast corrosion preparations.

Journal of Histochemistry & Cytochemistry ◽

10.1177/42.5.7908912 ◽

1994 ◽

Vol 42 (5) ◽

pp. 681-686 ◽

Cited By ~ 27

Author(s):

V Rummelt ◽

L M Gardner ◽

R Folberg ◽

S Beck ◽

B Knosp ◽

...

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Blood Vessels ◽

Tumor Cells ◽

Laser Scanning ◽

Three Dimensional ◽

Melanoma Cells ◽

Tumor Blood Vessels ◽

The Relationship ◽

Scanning Electron

The morphology of the microcirculation of uveal melanomas is a reliable market of tumor progression. Scanning electron microscopy of cast corrosion preparations can generate three-dimensional views of these vascular patterns, but this technique sacrifices the tumor parenchyma. Formalin-fixed wet tissue sections 100-150 microns thick from uveal melanomas were stained with the lectin Ulex europaeus agglutinin I (UEAI) and proliferating cell nuclear antigen (PCNA) to demonstrate simultaneously the tumor blood vessels and proliferating tumor cells. Indocarbocyanine (Cy3) was used as a fluorophore for UEAI and indodicarbocyanine (Cy5) was used for PCNA. Double labeled sections were examined with a laser scanning confocal microscope. Images of both stains were digitized at the same 5-microns intervals and each of the two images per interval was combined digitally to form one image. These combined images were visualized through voxel processing to study the relationship between melanoma cells expressing PCNA and various microcirculatory patterns. This technique produces images comparable to scanning electron microscopy of cast corrosion preparations while permitting simultaneous localization of melanoma cells expressing PCNA. The microcirculatory tree can be viewed from any perspective and the relationship between tumor cells and the tumor blood vessels can be studied concurrently in three dimensions. This technique is an alternative to cast corrosion preparations.

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The effect of PPAR?? ligands on the proliferation and apoptosis of human melanoma cells

Melanoma Research ◽

10.1097/00008390-200310000-00003 ◽

2003 ◽

Vol 13 (5) ◽

pp. 447-456 ◽

Cited By ~ 32

Author(s):

Wojciech Placha ◽

Dorota Gil ◽

Aldona Dembi??ska-Kie?? ◽

Piotr Laidler

Keyword(s):

Melanoma Cells ◽

Human Melanoma ◽

Human Melanoma Cells ◽

Proliferation And Apoptosis ◽

Ppar Ligands

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The principal neurons of the medial nucleus of the trapezoid body and NG2+ glial cells receive coordinated excitatory synaptic input

The Journal of General Physiology ◽

10.1085/jgp.200910194 ◽

2009 ◽

Vol 134 (2) ◽

pp. 115-127 ◽

Cited By ~ 48

Author(s):

Jochen Müller ◽

Daniel Reyes-Haro ◽

Tatjyana Pivneva ◽

Christiane Nolte ◽

Roland Schaette ◽

...

Keyword(s):

Glial Cell ◽

Glial Cells ◽

Synaptic Input ◽

Medial Nucleus ◽

Synaptic Structure ◽

Excitatory Synaptic Input ◽

Cell Processes ◽

To Receive ◽

Trapezoid Body ◽

Axosomatic Synapse

Glial cell processes are part of the synaptic structure and sense spillover of transmitter, while some glial cells can even receive direct synaptic input. Here, we report that a defined type of glial cell in the medial nucleus of the trapezoid body (MNTB) receives excitatory glutamatergic synaptic input from the calyx of Held (CoH). This giant glutamatergic terminal forms an axosomatic synapse with a single principal neuron located in the MNTB. The NG2 glia, as postsynaptic principal neurons, establish synapse-like structures with the CoH terminal. In contrast to the principal neurons, which are known to receive excitatory as well as inhibitory inputs, the NG2 glia receive mostly, if not exclusively, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor–mediated evoked and spontaneous synaptic input. Simultaneous recordings from neurons and NG2 glia indicate that they partially receive synchronized spontaneous input. This shows that an NG2+ glial cell and a postsynaptic neuron share presynaptic terminals.

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Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53

International Journal of Molecular Sciences ◽

10.3390/ijms19123952 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3952 ◽

Cited By ~ 14

Author(s):

Maria Mrakovcic ◽

Lauren Bohner ◽

Marcel Hanisch ◽

Leopold F. Fröhlich

Keyword(s):

Cell Death ◽

Tumor Cells ◽

Histone Deacetylase ◽

Stress Responses ◽

Histone Deacetylase Inhibitors ◽

Tumor Therapy ◽

Regulatory System ◽

Anticancer Activities ◽

Mutational Status

Tumor development and progression is the consequence of genetic as well as epigenetic alterations of the cell. As part of the epigenetic regulatory system, histone acetyltransferases (HATs) and deacetylases (HDACs) drive the modification of histone as well as non-histone proteins. Derailed acetylation-mediated gene expression in cancer due to a delicate imbalance in HDAC expression can be reversed by histone deacetylase inhibitors (HDACi). Histone deacetylase inhibitors have far-reaching anticancer activities that include the induction of cell cycle arrest, the inhibition of angiogenesis, immunomodulatory responses, the inhibition of stress responses, increased generation of oxidative stress, activation of apoptosis, autophagy eliciting cell death, and even the regulation of non-coding RNA expression in malignant tumor cells. However, it remains an ongoing issue how tumor cells determine to respond to HDACi treatment by preferentially undergoing apoptosis or autophagy. In this review, we summarize HDACi-mediated mechanisms of action, particularly with respect to the induction of cell death. There is a keen interest in assessing suitable molecular factors allowing a prognosis of HDACi-mediated treatment. Addressing the results of our recent study, we highlight the role of p53 as a molecular switch driving HDACi-mediated cellular responses towards one of both types of cell death. These findings underline the importance to determine the mutational status of p53 for an effective outcome in HDACi-mediated tumor therapy.

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BSCI-11. STROMAL PLATELET DERIVED GROWTH FACTOR RECEPTOR-β (PDGFRβ) PROMOTES BREAST CANCER BRAIN METASTASIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.009 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i3-i3

Author(s):

Katie Thies ◽

Anisha Hammer ◽

Blake Hildreth ◽

Luke Russell ◽

Steven Sizemore ◽

...

Keyword(s):

Breast Cancer ◽

Growth Factor ◽

Brain Metastasis ◽

Brain Metastases ◽

Tumor Cells ◽

Mammary Tumor ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Mammary Tumor Cells ◽

The Brain

Abstract Stromal platelet-derived growth factor receptor-beta (PDGFRβ) has emerged as an actionable mediator of breast tumor-stromal communication. As a receptor tyrosine kinase, PDGFRβ is activated by its ligand, PDGFB, which is released by neighboring tumor epithelium and endothelium. However, how PDGF signaling mediates breast cancer (BC) initiation, progression, and metastasis remains unclear. To evaluate PDGFRβ in this disease, we developed a mouse model of stromal-specific PDGFRβ activation using the Fsp-cre transgene previously published by our group. Mesenchymal-specific activation of PDGFRβ promotes preferential experimental brain metastasis of PDGFB-expressing mammary tumor cells when injected intravenously and accelerates intracranial tumor growth of these cells. Mammary tumor cells expressing low levels of PDGFB do not exhibit a similar increase in brain metastases in PDGFRβ mutant mice. To our knowledge, this is the first example where genetic manipulation of the stroma leads to an increased incidence of BCBM. Our pre-clinical data suggests that primary breast tumors that express high PDGFB could preferentially metastasize to the brain. To test this in patients, we analyzed PDGFB protein expression in a tissue microarray comprised of HER2-positive and triple negative BC primary tumors. While high PDGFB did not correlate with site-independent metastatic recurrence, it was prognostic of brain metastasis, mirroring our mouse data. Our findings suggest that high primary tumor PDGFB expression defines a subset of BC patients predisposed to brain metastases. These patients may benefit from therapeutic intervention of PDGFRβ signaling. To test this pre-clinically, we treated mice harboring intracranial tumors with the PDGFR-specific inhibitor, crenolanib. Excitingly, crenolanib treatment significantly inhibited the brain tumor burden in these mice. Combined, our findings (1) advocate that primary tumor expression of PDGFB is a novel prognostic biomarker for the development of BCBM and (2) support clinical trial evaluation of PDGFR inhibitors for the prevention and treatment of BCBM.

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