Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA136237 | ENA |
REPOSITORIES: ENA
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Project description:Melanoma growth is driven by malignant melanoma initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member, ABCB5. ABCB5+ melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE-1 and are associated with CD31-negative vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5+ MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5+ tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced in a VEGFR-1-dependent manner expression of CD144 in ABCB5+ subpopulations that constitutively expressed VEGFR-1, but not in ABCB5- bulk populations that were predominantly VEGFR-1-negative. In vivo, melanomaspecific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5+ VM morphology and inhibited ABCB5+ VM-associated production of the secreted melanoma mitogen, laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results demonstrate that VEGFR-1 function in MMIC regulates VM and associated laminin production, and show that this function represents one mechanism through which MMIC promote tumor growth.
2011-01-13 | GSE26569 | GEO
Project description:Melanoma growth is driven by malignant melanoma initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member, ABCB5. ABCB5+ melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE-1 and are associated with CD31-negative vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5+ MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5+ tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced in a VEGFR-1-dependent manner expression of CD144 in ABCB5+ subpopulations that constitutively expressed VEGFR-1, but not in ABCB5- bulk populations that were predominantly VEGFR-1-negative. In vivo, melanomaspecific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5+ VM morphology and inhibited ABCB5+ VM-associated production of the secreted melanoma mitogen, laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results demonstrate that VEGFR-1 function in MMIC regulates VM and associated laminin production, and show that this function represents one mechanism through which MMIC promote tumor growth. Microarray analyses were performed on purified ABCB5+ (n=5) and ABCB5- (n=5) cell subsets derived from the established human melanoma cell lines G3361 and A375 and from three distinct clinical melanoma specimen. Total RNA was extracted, processed and hybridized onto Affymetrix human HG-U133Plus2 GeneChip microarrays (Affymetrix, Santa Clara, CA).
2011-01-13 | E-GEOD-26569 | biostudies-arrayexpress
Project description:Growth inhibition of ovarian tumor-initiating cells by niclosamide
| PRJNA153081 | ENA
Project description:Voluntary exercise reduces the risk of cancer and lowers the risk of disease recurrence. Yet the mechanisms for this protection remain to be elucidated. Here we demonstrate that exercise halves tumor growth through an exercise-dependent mobilization and intratumoral infiltration of NK cells in malignant melanoma. Using voluntary wheel running, we show that exercise prior to and during B16 tumor challenge reduced tumor growth by 67%, and this reduction was associated with increased inflammation and immune cell infiltrates, especially NK cells, in the tumors from exercising mice. Depletion of NK cells blunted the exercise-dependent reduction in tumor growth. Moreover, during exercise, NK cells were engaged through an epinephrine-dependent mobilization to the circulation and redistributed to peripheral tissues through an IL-6 dependent mechanism. This study highlights the importance of exercise-dependent immune regulation in the control of malignant melanoma Gene expression profile of melanoma tumor tissue from two groups of exercise and non-exercise mice
2016-07-21 | E-GEOD-62628 | biostudies-arrayexpress
Project description:Over the last decades, exosomes have received increasing attention due to their involvement in numerous pathologies including cancer. Tumor-derived exosomes and exosomes derived from the tumor microenvironment are implicated in multiple mechanisms that support disease progression such as the escape of malignant cells from immunosurveillance, tumor cell growth, tumor angiogenesis, preparation of a pre-metastatic niche and remodeling of the extracellular matrix, thereby promoting dissemination and metastasis. Here, we performed protein expression phenotyping of exosomes derived from different invasive and proliferative melanoma cell lines (n=8) to provide a solid framework of gene expression programs, which - in a clinical setting - would be useful for prognosis and may also predict treatment response. Cell line characteristics have been published previously (Wenzina et al.,2020). Having identified a set of differentially expressed proteins in proliferative and invasive melanoma cell lines, we correlated them to the protein composition of plasma exosomes from melanoma patients pre and post immunotherapy treatment (n=7) as well as healthy controls (n=5).
2022-07-14 | PXD025475 | Pride
Project description:The acquisition of cell invasiveness is the key transition from benign melanocyte hyperplasia to aggressive melanoma. Recent work using non-melanoma cancer cells has provided an intriguing new link between the presence of supernumerary centrosomes and increased cell invasion. Moreover, supernumerary centrosomes were shown to drive non-cell-autonomous invasion of cancer cells. Although centrosomes are the principle microtubule organizing centers the role of dynamic microtubules for non-cell-autonomous invasion remains unexplored, in particular in melanoma. We investigated the role of supernumerary centrosomes and dynamic microtubules in melanoma cell invasion and found that highly invasive melanoma cells are characterized by the presence of supernumerary centrosomes and by increased microtubule growth rates, both of which are functionally interlinked. We demonstrate that enhanced microtubule growth is required for increased 3D melanoma cell invasion. Moreover, we show that the activity to enhance microtubule growth can be transferred to adjacent non-invasive cells through extracellular vesicles harboring HER2 that are required for increased cell invasion of melanoma cells into 3D matrices. Hence, our study suggests that suppressing microtubule growth, either directly using anti-microtubule drugs or through HER2 inhibitors might be therapeutically beneficial to inhibit cell invasiveness and thus, metastasis of malignant melanoma.
2022-04-27 | PXD032224 | Pride
Project description:IGFBP5, a critical regulators of insulin-like growth factors, has been reported to be involved in many kinds of carcinogenesis and cancer metastases. The role of IGFBP5 in human malignant melanoma (MM), however, remains largely unknown. In this study, we demonstrated that IGFBP5 was aberrantly expressed in human melanoma cells and cancer tissues. Overexpression of IGFBP5 dramatically inhibited the proliferation, migration and invasion of human melanoma cells, whereas knockdown of IGFBP5 by shRNA resulted in the opposite effects, enhanced the cell proliferation, migration and metastasis. In addition, IGFBP5 overexpression suppressed the growth and metastasis of melanoma xenograft tumor in vivo and IGFBP5 overexpression inhibited epithelialâmesenchymal transition (EMT) phenotype and stem cell property of tumor cell, with decreased expression of HIF1α, E-cadherin and stem cell markers NANOG, SOX2, OCT4, KLF4 and CD133. Moreover, IGFBP5 exhibited its growth inhibitory activity through inhibition of extracellular signal-regulated Kinase (ERK) and P38-MAPK signaling pathway. Taken together, our findings indicate that IGFBP5 acts as tumor suppressor roles in MM through the modulation of ERK1/2 and P38-MAPK signaling pathway as well as EMT procession and cell stemness, suggesting IGFBP5 as a novel target for human melanoma diagnosis and therapy. mRNA profiles of IGFBP5 over expression (OE) in A375 and A375 cell line were generated using Ion torrent
2016-01-05 | E-GEOD-64693 | biostudies-arrayexpress
Project description:Voluntary exercise reduces the risk of cancer and lowers the risk of disease recurrence. Yet the mechanisms for this protection remain to be elucidated. Here we demonstrate that exercise halves tumor growth through an exercise-dependent mobilization and intratumoral infiltration of NK cells in malignant melanoma. Using voluntary wheel running, we show that exercise prior to and during B16 tumor challenge reduced tumor growth by 67%, and this reduction was associated with increased inflammation and immune cell infiltrates, especially NK cells, in the tumors from exercising mice. Depletion of NK cells blunted the exercise-dependent reduction in tumor growth. Moreover, during exercise, NK cells were engaged through an epinephrine-dependent mobilization to the circulation and redistributed to peripheral tissues through an IL-6 dependent mechanism. This study highlights the importance of exercise-dependent immune regulation in the control of malignant melanoma
2016-07-21 | GSE62628 | GEO
Project description:Exosomes (40–100 nm) are organelle-like membranous structures shed into interstitial spaces and body fluids under diverse pathophysiologic conditions, including tumor development. The tumor microenvironment is abundant with exosomes secreted by the cancer cells themselves. Studies have shown that tumor-derived exosomes can transport RNA and active molecules to other cells to promote tumor growth. Exosomes are increasingly being recognized as a major contributor in the progression of malignant neoplasms. We have found that normal melanocytes can acquire invasiveness through the internalization of melanoma cell-derived exosomes. However, little is known about how the exosomes modulate the melanocytes in the microenvironment to optimize conditions for tumor progression and metastasis. We hypothesize that melanoma cell-derived exosomes can drive the dysregulation of transcriptomes in normal melanocytes and facilitate melanoma progression. Our objective is to identify differentially expressed genes in melanocytes driven by tumor cell-derived exosomes through RNA sequencing and translate those genes as therapeutic targets for melanoma metastasis.
2019-11-06 | GSE84683 | GEO