Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular profiling of lymphatic endothelial cells activation in vitro

ABSTRACT: The lymphatic vascular system plays a key role in cancer progression. Indeed, the activation of lymphatic endothelial cells (LECs) through the lymphangiogenic process allows the formation of new lymphatic vessels (LVs) that represent the major route for dissemination of solid tumors. This process is governed by a plethora of cancer-derived and microevironmental mediators that strictly activate and control specific molecular pathways in LECs. In this work we used an in vitro model of LEC activation to trigger lymphangiogenesis using a mix of recombinant pro-lymphangiogenic factors (VFS) and a co-culture system with human melanoma cells. Both systems efficiently activated LECs, and under these experimental conditions RNA sequencing was exploited to unveil the transcriptional profile of activated LECs. Our data demonstrate that both recombinant and tumor cell-mediated activation trigger significant molecular pathways associated with endothelial activation, morphogenesis and cytokine-mediated signaling. In addition, this system provides information on new genes to be further investigated in the lymphangiogenesis process and open the possibility for further exploitation in other tumor contexts where lymphatic dissemination plays a relevant role.

ORGANISM(S): Homo sapiens

PROVIDER: GSE247178 | GEO | 2023/12/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from Control and Six1 expressing MCF7 derived xenograft tumors

Project description:Although an important association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago, an active role for the lymphatic system in metastatic dissemination has only recently been examined. We demonstrate that the Six1 homeoprotein promotes peri- and intra-tumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. We identify the pro-lymphangiogenic factor, VEGF-C, as required for this process, and demonstrate transcriptional induction as the mechanism of regulation of VEGF-C expression by Six1. Using a different, but complementary animal model, we show that while required, VEGF-C is not sufficient for the pro-metastatic effects of Six1. Verifying the clinical significance of this pro-metastatic Six1-VEGF-C axis, we demonstrate co-expression of Six1 and VEGF-C in human breast cancer. Two Control and two Six1 expressing MCF7 clones were orthotopically injected into NOD/Scid mice forming a total of 3 Control and 3 Six1 tumors that were allowed to grow to 2 cm^3 . The tumors were dissected and total RNA was isolated from each tumor and hybridized to Affymetrix arrays

2012-03-31 | E-GEOD-35314 | biostudies-arrayexpress

Metabolomics revealed the influence of breast cancer on lymphatic endothelial cell metabolism, metabolic crosstalk, and lymphangiogenic signaling in co-culture

Project description:<p>Breast cancer metastasis occurs via blood and lymphatic vessels. Breast cancer cells 'educate' lymphatic endothelial cells (LECs) to support tumor vascularization and growth. However, despite known metabolic alterations in breast cancer, it remains unclear how lymphatic endothelial cell metabolism is altered in the tumor microenvironment and its effect in lymphangiogenic signaling in LECs. We analyzed metabolites inside LECs in co-culture with MCF-7, MDA-MB-231, and SK-BR-3 breast cancer cell lines using 1H nuclear magnetic resonance (NMR) metabolomics, Seahorse, and the spatial distribution of metabolic co-enzymes using optical redox ratio imaging to describe breast cancer-LEC metabolic crosstalk. LECs co-cultured with breast cancer cells exhibited cell-line dependent altered metabolic profiles, including significant changes in lactate concentration in breast cancer co-culture. Cell metabolic phenotype analysis using Seahorse showed LECs in co-culture exhibited reduced mitochondrial respiration, increased reliance on glycolysis and reduced metabolic flexibility. Optical redox ratio measurements revealed reduced NAD(P)H levels in LECs potentially due to increased NAD(P)H utilization to maintain redox homeostasis. 13C-labeled glucose experiments did not reveal lactate shuttling into LECs from breast cancer cells, yet showed other 13C signals in LECs suggesting internalized metabolites and metabolic exchange between the two cell types. We also determined that breast cancer co-culture stimulated lymphangiogenic signaling in LECs, yet activation was not stimulated by lactate alone. Increased lymphangiogenic signaling suggests paracrine signaling between LECs and breast cancer cells which could have a pro-metastatic role.</p>

2024-06-25 | MTBLS859 | MetaboLights

Expression data from Control and Six1 expressing MCF7 derived xenograft tumors

2012-04-01 | GSE35314 | GEO

Bianchi2015 -Model for lymphangiogenesis in normal and diabetic wounds

Project description:Arianna Bianchi, Kevin J. Painter & Jonathan A. Sherratt. A mathematical model for lymphangiogenesis in normal and diabetic wounds. Journal of Theoretical Biology 383 (2015). Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis) very few have been proposed for the regeneration of the lymphatic network. Moreover, lymphangiogenesis is markedly distinct from angiogenesis, occurring at different times and in a different manner. Here a model of five ordinary differential equations is presented to describe the formation of lymphatic capillaries following a skin wound. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from experimental and clinical data. The system is then solved numerically and the results are compared with the available biological literature. Finally, a parameter sensitivity analysis of the model is taken as a starting point for suggesting new therapeutic approaches targeting the enhancement of lymphangiogenesis in diabetic wounds. The work provides a deeper understanding of the phenomenon in question, clarifying the main factors involved. In particular, the balance between TGF-β and VEGF levels, rather than their absolute values, is identified as crucial to effective lymphangiogenesis. In addition, the results indicate lowering the macrophage-mediated activation of TGF-β and increasing the basal lymphatic endothelial cell growth rate, inter alia, as potential treatments. It is hoped the findings of this paper may be considered in the development of future experiments investigating novel lymphangiogenic therapies.

2024-09-02 | BIOMD0000000722 | BioModels

Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through a NGFR-dependent mechanism

Project description:Secreted extracellular vesicles are known to influence the tumor microenvironment and promote metastasis. In this work, we have analyzed the involvement of extracellular vesicles in the establishment of lymph node pre-metastatic niches by melanoma cells. We found that small extracellular vesicles (sEVs) derived from highly metastatic melanoma cell lines spread broadly through the lymphatic system and were taken up by lymphatic endothelial cells, reinforcing lymph node metastasis. Melanoma-derived sEVs induce lymphangiogenesis, a hallmark of pre-metastatic niche formation, in vitro and in lymphoreporter mice in vivo. We found that neural growth factor receptor (NGFR) is secreted in melanoma-derived small extracellular vesicles and shuttled to lymphatic endothelial cells, inducing lymphangiogenesis and tumor cell adhesion through the activation of ERK and NF-B pathways and ICAM1 expression. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased melanoma lymph node metastasis and extended the survival. Importantly, analysis of NGFR expression in lymph node metastases and matched primary tumors shows that levels of MITF+NGFR+ lymph node metastatic cells are correlated with disease outcome. Our data support the idea that NGFR secreted in sEVs favors lymph node pre-metastatic niche formation and lymph node metastasis in melanoma

2021-08-05 | PXD024852 | Pride

Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis by a NGFR-dependent mechanism

Project description:Secreted extracellular vesicles are known to influence the tumor microenvironment and promote metastasis. In this work, we have analyzed the involvement of extracellular vesicles in establishing the lymph node pre-metastatic niche by melanoma cells. We found that small extracellular vesicles (sEVs) derived from highly metastatic melanoma cell lines spread broadly through the lymphatic system and are taken up by lymphatic endothelial cells reinforcing lymph node metastasis. Melanoma-derived sEVs induce lymphangiogenesis, a hallmark of pre-metastatic niche formation, in vitro and in lymphoreporter mice in vivo. Analysis of involved factors demonstrated that the neural growth factor receptor (NGFR) is secreted in melanoma-derived small extracellular vesicles and shuttled to lymphatic endothelial cells inducing lymphangiogenesis and tumor cell adhesion through the activation of ERK and NF-B pathways and ICAM1 expression. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased melanoma lymph node metastasis and extended mice survival. Importantly, analysis of NGFR expression in lymph node metastases and matched primary tumors shows that levels of MITF+NGFR+ lymph node metastatic cells are correlated with disease outcome. Our data support that NGFR is secreted in sEVs favoring lymph node pre-metastatic niche formation and lymph node metastasis in melanoma.

2021-07-16 | PXD024108 | Pride

Profiling of filarial induced genes in lymphatic endothelial cells

Project description:To observe the global changes in the lymphatic endothelial cells upon exposure to filarial antigens or parasites, LECs were stimulated for 24, 48, and 72hrs and the expression profiles were carried out. Human filarial parasites Brugia malayi and Wuchereria bancrofti habitat the lymphatics and cause lymphatic dilatation and lymphedema. In order to evaluate the effect of various stage specific effects on the lymphatic endothelial cells (LEC) and understand how they modulate the lymphatic dysfunction, LECs were stimulated in antigens derived from the Brugia malayi. These are preliminary time course data towards understanding how the filarial antigens induce lymphangiogenesis.

2010-05-19 | E-GEOD-15454 | biostudies-arrayexpress

Lymphatic-derived 25-hydroxycholesterol promotes immunity in melanoma by inhibiting PPAR-γ in tumor associated macrophages and monocytes

Project description:In melanoma, lymphangiogenesis correlates with metastasis and poor prognosis and promotes immunosuppression. However, it also potentiates immunotherapy by supporting trafficking of immune cells. Lymphatic endothelial cells (LECs) are highly plastic cells that shape their phenotype according to distinct microenvironments, which likely define their functional properties, such as immunomodulation. Here, we show in a lymphangiogenic murine melanoma model that LECs upregulate the enzyme Ch25h, which catalyzes the formation of 25-hydroxycholesterol (25-HC) from cholesterol and plays important roles in regulating lipid metabolism, gene expression, and immune activation. LECs represent the main source of extracellular 25-HC in tumors, leading to the inhibition of PPAR- in intra-tumoral macrophages and monocytes. This prevents their immunosuppressive phenotype and instead promotes their conversion into proinflammatory myeloid cells that support effector T cell functions. We identify here in mechanistic detail a novel LEC function that supports anti-tumor immunity, which can be therapeutically exploited in combination with immunotherapy.

2024-11-21 | GSE242026 | GEO

Lymphatic-derived 25-hydroxycholesterol promotes immunity in melanoma by inhibiting PPAR-γ in tumor associated macrophages and monocytes

2024-11-21 | GSE239972 | GEO

Lymphatic-derived 25-hydroxycholesterol promotes immunity in melanoma by inhibiting PPAR-γ in tumor associated macrophages and monocytes

2024-06-30 | GSE242150 | GEO