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TRAP1 expression elicits pro-tumoral functions in macrophages associated to malignant peripheral nerve sheath tumor cells

ABSTRACT: TRAP1 expression elicits pro-tumoral functions in macrophages associated to malignant peripheral nerve sheath tumor cells

PROVIDER: PRJNA1246121 | ENA |

REPOSITORIES: ENA

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TRAP1 expression elicits pro-tumoral functions in macrophages associated to malignant peripheral nerve sheath tumor cells

Project description:Metabolic adaptations can sustain the pro-neoplastic functions exerted by macrophages in the tumor microenvironment. Malignant peripheral nerve sheath tumors (MPNSTs), aggressive and incurable sarcomas that develop either sporadically or in the context of the genetic syndrome Neurofibromatosis type 1, are highly infiltrated by macrophages, whose contribution to MPNST growth remains poorly characterized. Here, we analyze the role played by the molecular chaperone TRAP1, a regulator of mitochondrial metabolic pathways, in shaping the pro-tumoral activity of macrophages associated to MPNST cells. We have studied the phenotypic changes elicited by a MPNST cell-conditioned medium in macrophages with or without TRAP1, and their subsequent ability to support MPNST cell growth and migration and endothelial cell angiogenesis. The presence of TRAP1 is required in both naive and M2-like macrophages for eliciting phenotypic changes that lead to the acquisition of pro-neoplastic features. TRAP1-expressing macrophages become able to sustain MPNST cell growth and migration and to exert pro-angiogenic properties on endothelial cells through accumulation of the metabolite succinate and the ensuing activation of a HIF-1α-dependent transcriptional program. Our data provide evidence of a molecular crosstalk between MPNST cellular components, in which soluble factors released by cancer cells drive phenotypic changes in macrophages that in turn enhance pro-tumoral biological routines in both MPNST and endothelial cells. TRAP1-dependent metabolic rewiring in macrophages is mandatory for sustaining this interplay, as a TRAP1-succinate-HIF-1α signaling axis orchestrates their acquisition of tumor-promoting features.

2025-09-03 | GSE293735 | GEO

Methylation profiling of malignant peripheral nerve sheath tumour samples

Project description:Methylation profiling of malignant peripheral nerve sheath tumours (MPNSTs), epithelioid MPNSTs, sarcoma NOS, melanomas and spindle cell/sclerosing rhabdomyosarcomas.

2020-07-02 | E-MTAB-8864 | biostudies-arrayexpress

Malignant peripheral nerve sheath tumor (MPNST) tumor samples

Project description:Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma. Comprehensive proteomic profiles of 23 MPNST tumor specimens were obtained using LC-MS/MS. Among 23 tumor specimens, 13 patients showed favorable prognosis and 10 did local recurrence/distant metastasis.

2022-12-22 | PXD030585 | JPOST Repository

Comparative genomic hybridization of human malignant peripheral nerve sheath tumors and normal reference DNA

Project description:DNA copy number profiling of malignant peripheral nerve sheath tumours

2009-02-25 | E-MEXP-869 | biostudies-arrayexpress

Comparison of modified rectus sheath nerve block and transverse abdominal fascia block in laparoscopic radical resection of colorectal cancer

Project description:Interventions: Bilateral transverse abdominal fascia block combined with general anesthesia group (DTAP):Rectus abdominis sheath nerve block based on surgical incision combined with general anesthesia;Incision-based rectus sheath nerve block combined with general anesthesia group (MSRA):Rectus abdominis sheath nerve block combined with general anesthesia based on surgical incision Primary outcome(s): the dose of remifentanil Study Design: Parallel

| 2725611 | ecrin-mdr-crc

Canine Cutaneous Peripheral Nerve Sheath Tumours versus Fibrosarcomas can be Differentiated by Neuroectodermal Marker Genes in their Transcriptome.

Project description:The diagnostic differentiation of canine fibrosarcomas and peripheral nerve sheath tumors (PNST) is mainly based on their histopathologic phenotype. Histologic differentiation of these tumors can, however, be difficult and there is a lack of immunohistochemical markers to prove their histogenic origin. To identify possible PNST markers and to further investigate the histogenic origin of the two tumor types, we compared histologically defined canine fibrosarcomas and peripheral nerve sheath tumors by microarray analysis. Forty-five annotated gene products were significantly differentially expressed in both tumor types. Seven of these gene products, known to be specifically expressed in neuroectodermal tissues, showed higher expression in peripheral nerve sheath tumors: FMN2, KIF1B, GLI1, ROBO1, NMUR2, DOK4 and HMG20B. Furthermore, eight genes associated with carcinogenesis were up-regulated in fibrosarcomas: FHL2, PLAGL1, FNBP1L, BAG2, HK1, CSK and Cox5A. Comparison of the fibrosarcoma and PNST transcriptome therefore identified PNST phenotype-associated genes involved in neuroectodermal differentiation which may be potential PNST markers. Furthermore, the identified fibrosarcoma phenotype-associated genes may be potential markers to differentiate fibrosarcomas from other tumor types and may be involved in their pathogenesis. The aim of the present study was to examine the differences in global gene expression of histologically prototypic fibrosarcomas and PNST. To this end, complete transcriptome microarray analyses were used to quantify differences in gene expression activity in both tumor types.

2012-10-30 | E-GEOD-34382 | biostudies-arrayexpress

MicroRNA expression profiles in malignant peripheral nerve sheath tumors

Project description:MicroRNA expression profiles in malignant peripheral nerve sheath tumors

| PRJNA591614 | ENA

Targeting RABL6A-RB1 signaling suppresses malignant peripheral nerve sheath tumors

Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin dependent kinases (CDKs), commonly through loss of CDK inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor-based therapy in MPNSTs.

2020-02-11 | GSE145064 | GEO

Canine Cutaneous Peripheral Nerve Sheath Tumours versus Fibrosarcomas can be Differentiated by Neuroectodermal Marker Genes in their Transcriptome.

2012-10-30 | GSE34382 | GEO

Effects of different ventilation modes on the diameter of optic nerve sheath in elderly patients undergoing laparoscopic colorectal cancer surgery

Project description:Interventions: P:Pressure control ventilation;V:Volume control ventilation Primary outcome(s): Diameter of optic nerve sheath Study Design: Parallel

| 2694450 | ecrin-mdr-crc

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