Pericytes in Sarcomas and Other Mesenchymal Tumors

Chang, Leslie; Scott, Michelle; Meyers, Carolyn A.; James, Aaron W.

doi:10.1007/978-3-030-16908-4_4

Cited by 13 publications

(12 citation statements)

References 61 publications

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“…No definitive histological features suggesting origination from vessels or nerves (besides whorling around central unidentifiable structures) was observed. However, to determine whether gene expression could further distinguish the tumors histologically identified as PNST/PWTs, the expression of pericyte markers was extracted (31). No significant up-regulation of these 17 genes were observed (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

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Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations inTP53, KMTgenes andPDGFBfusions

Das

Idate

Lana

et al. 2023

Preprint

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Canine soft tissue sarcomas (STS) are a heterogenous group of malignant tumors arising from mesenchymal cells of soft tissues. This simplified collective of tumors most commonly arise from subcutaneous tissues, are treated similar clinically, and conventionally exclude other sarcomas with more definitive anatomical, histological, or biological features. Histologically, canine STS sub-types are difficult to discern at the light microscopic level due to their overlapping features. Thus, genomic, and transcriptomic profiling of canine STS may prove valuable in differentiating the diverse sub-types of mesenchymal neoplasms within this group. To this purpose we sought to characterize the transcript expression and genomic mutation profiles of canine STS. To delineate transcriptomic sub-types, hierarchical clustering was used to identify 4 groups with district expression profiles. Using the RNAseq data, we identified three samples carrying driver fusions of platelet derived growth factor B (PDGFB) and collagen genes. Sensitivity to imatinib was evaluated in a canine STS cell line also bearing a PDGFB fusion. Using whole exome sequencing, recurrent driver variants were identified in the cancer genes KMT2D (21% of the samples) and TP53 (21%) along with copy number losses of RB1 and CDKN2A. Gene amplifications and resulting transcript increases were identified in genes on chromosomes 13, 14, and 36. A subset of STS was identified with high T-cell infiltration. This multi-omics approach has defined canine STS sub-types at a molecular level for comparison to their human counterparts, to improve diagnosis, and may provide additional targets for therapy.

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Section: Resultsmentioning

confidence: 99%

“…However, to determine whether gene expression could further distinguish the tumors histologically identified as PNST/PWTs, the expression of pericyte markers was extracted (31). No significant up-regulation of these 17 genes were observed (Supplementary Fig.…”

Section: Canine Patients and Tumor Overviewmentioning

confidence: 99%

Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations inTP53, KMTgenes andPDGFBfusions

Das

Idate

Lana

et al. 2023

Preprint

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“…In the current study, a subgroup of RGS5 + /PDGFRA − stromal cells showed high expression of PDGFRB, MYH11, MCAM, and angiopoietin ANGPT2, suggesting that these stromal cells were pericytes in urothelial tissues. [ 50 ] These results highlight the heterogeneous nature of stromal cells and their tumor-supportive roles in the urothelial TME, which may serve as potential therapeutic targets in UC.…”

Section: Discussionmentioning

confidence: 96%

Single-cell transcriptomic analysis of tumor heterogeneity and intercellular networks in human urothelial carcinoma

Jin

Wang

Luo

et al. 2023

Chinese Medical Journal

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Background: Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies. Methods: Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly. Results: Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 + /ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion: Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.

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“…14 This suggests that pericytes may also contribute to malignancies through perivascular invasion and atypical interactions with endothelial cells. [15][16][17] However, this is only observed in diseased vessels and may not apply to normal conditions.…”

Section: Discussionmentioning

confidence: 99%

Differential pericyte marker expression in craniofacial benign and malignant vascular tumors

Chandra

et al. 2023

J Oral Pathology Medicine

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BackgroundVascular anomalies and tumors are common in the head, neck, and craniofacial areas and are associated with abnormalities in the angiomatous architecture. However, the etiology and molecular basis for the pathogenesis of most vascular lesions are still unknown. Pericytes are mural cells that surround endothelial cells. Besides angiogenesis and other physiological functions, pericytes play an important role in vascularized tissue repair and as resident mesenchymal stem/progenitor cells. Perivascular cells demonstrate a distinct immunohistochemical profile, including expression of alpha‐smooth muscle actin (α‐SMA), CD146, CD105, and PDGFRβ, without endothelial differentiation (absence of CD31 and CD34 immunoreactivity). These pericyte markers have been shown to be expressed in soft tissue hemangiomas. However, they have not been fully examined in intraosseous hemangiomas.MethodsIn this study, we compared mesenchymal stem cell (MSC) expression of CD146 and α‐SMA markers in pericytes from hemangiomas from different tissues and malignant vascular tumors.ResultsThe results demonstrated an increased expression of pericyte markers in perivascular cells of benign hemangiomas, especially intraosseous hemangiomas and a significantly reduced expression of pericyte markers in malignant angiosarcomas.ConclusionThe evidence provides insight into the function of pericytes in vascular tumors and suggests their role in vascular tumor disease types.

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Pericytes in Sarcomas and Other Mesenchymal Tumors

Cited by 13 publications

References 61 publications

Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations inTP53, KMTgenes andPDGFBfusions

Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations inTP53, KMTgenes andPDGFBfusions

Single-cell transcriptomic analysis of tumor heterogeneity and intercellular networks in human urothelial carcinoma

Differential pericyte marker expression in craniofacial benign and malignant vascular tumors

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