Defining the Extracellular Matrix of Rhabdomyosarcoma

Lian, Xiaolei; Bond, Jaqueline; Bharathy, Narendra; Boudko, Sergei P.; Pokidysheva, Elena; Shern, Jack F.; Lathara, Melvin; Sasaki, Takako; Settelmeyer, Teagan P.; Cleary, Megan M.; Bajwa, Ayeza; Srinivasa, Ganapati; Hartley, Christopher; Bächinger, Hans Peter; Mansoor, Atiya; Gultekin, Sakir H.; Berlow, Noah; Keller, Charles

doi:10.3389/fonc.2021.601957

Cited by 13 publications

(8 citation statements)

References 34 publications

(45 reference statements)

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“…Fibrillin-2 (FBN2), first expressed at the site of contact between epithelial and mesenchymal cells, is an extracellular calcium-binding microfibril involved in multiple biological pathways, including bone mineralization, osteoblast maturation, and calcium-binding ( 28 ). It has been identified as a diagnostic biomarker for smooth muscle sarcoma and rhabdomyosarcoma ( 29 , 30 ). However, studies on FBN2 have focused on its methylation, and aberrant methylation of FBN2 has been found in breast cancer, non-small cell lung cancer, and esophageal squamous cell carcinoma ( 31 – 33 ), and the promoter region of the FBN2 gene has been repeatedly reported to be hypermethylated in several types of cancer.…”

Section: Discussionmentioning

confidence: 99%

miR-139-5p Was Identified as Biomarker of Different Molecular Subtypes of Breast Carcinoma

Sun¹,

Dai²,

Chen³

et al. 2022

Front. Oncol.

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Located on chromosome 11q13.4, miR-139-5p has been confirmed by several studies as a possible attractive biomarker for cancer, including breast cancer, but its mechanism of correlation in different molecular subtypes of breast cancer has not been reported. In this study, comprehensive bioinformatics analysis was used to evaluate the expression of miR-139-5p in different molecular subtypes of breast cancer (luminal A, luminal B, HER2-enriched, and basal-like). The target genes of miR-139-5p were predicted by using an online database TargetScan and miRDB, and three key genes, FBN2, MEX3A, and TPD52, were screened in combination with differentially expressed genes in different molecular subtypes of breast cancer. The expression of the three genes was verified separately, and the genes were analyzed for pathway and functional enrichment. Bone marrow mesenchymal stem cells (BMSC) are another kind of highly plastic cell population existing in bone marrow besides hematopoietic stem cells. BMSC can affect the proliferation and migration of cancer cells, promote the metastasis and development of cancer, and regulate the tumor microenvironment by secreting exosome mirnas, thus affecting the malignant biological behavior of tumor cells. Finally, human bone marrow mesenchymal stem cells exosomes were obtained by ultracentrifugation, and the morphology of exosomes was observed by transmission electron microscopy. The expression of miR-139-5p in normal breast cells MCF-10A, human breast cancer cell line MDA-MB-231 cells, and BMSCs-derived exosomes were compared; the exosomes and MDA-MB-231 cells were co-cultured to observe their effects on the proliferation of the MDA-MB-231 cells. Human bone marrow mesenchymal stem cell-derived exosomes inhibited the growth of breast cancer cells and promoted the expression of FBN2, MEX3A, and TPD52 by transporting miR-139-5p.

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Section: Discussionmentioning

confidence: 99%

miR-139-5p Was Identified as Biomarker of Different Molecular Subtypes of Breast Carcinoma

Sun¹,

Dai²,

Chen³

et al. 2022

Front. Oncol.

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“…Most previous studies focused on events that happened within tumor cells, several recent studies addressed the role of the microenvironment in tumor tissue components when stimulating tumor progression, invasion, and metastasis 29,30 . The mechanism of tumor–stroma interaction is of therapeutic importance.…”

Section: Discussionmentioning

confidence: 99%

DWI and IVIM Imaging in a Murine Model of Rhabdomyosarcoma: Correlations with Quantitative Histopathologic Features

Fang

Yang

Chen

et al. 2021

Magnetic Resonance Imaging

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Background High cellularity and abnormal interstitial structures are some of the unfavorable factors that affect the treatment outcomes and survival of rhabdomyosarcoma (RMS) patients. Purpose To explore the correlation between diffusion‐weighted imaging (DWI) and intravoxel incoherent motion (IVIM) with quantitative histopathologic features in a murine model of RMS. Study Type Prospective. Animal Model Murine model of RMS (31 female BALB/c nude mice). Field Strength/Sequence 3.0 T; fast spin‐echo (FSE) T1‐weighted imaging, fast relaxation fast spin‐echo (FRFSE) T2‐weighted imaging, DWI PROPELLER FSE imaging sequence, and IVIM echo planar imaging sequence; 10 different b‐values (0, 50, 100, 150, 200, 400, 600, 800, 1000, and 1200 s/mm2). Assessment Magnetic resonance imaging (MRI) was performed after 30–45 days of implantation. The following MRI parameters were calculated: apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo‐diffusion coefficient (D*), and perfusion fraction (f). Histopathologic features, which contained nuclear, cytoplasmic, and stromal fractions, and the nuclear‐to‐cytoplasmic ratio within the tumor were measured using image‐based segmentation. Statistical Tests Pearson's correlation, multiple linear regression analysis, and receiver operating characteristic curve analysis were performed. A P < 0.05 was considered statistically significant. Results The ADC value showed moderate negative correlation with nuclear fraction (r = −0.540), and moderate positive correlation with stroma fraction (r = 0.474). The D value showed moderate negative correlation with nuclear fraction (r = −0.491), and moderate positive correlation with stroma fraction (r = 0.421). The f value showed a moderate negative correlation with stroma fraction (r = −0.423). The D value showed the best diagnostic ability. The optimal cut‐off D value of 0.460 was associated with 77.8% sensitivity and 68.2% specificity (area under the curve, 0.747). Data Conclusion The ADC, D, and f values obtained from DWI and IVIM images showed moderate correlation with the quantitative histopathologic features in a murine model of RMS. Level of Evidence 1 Technical Efficacy Stage 3

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“…Given previous studies suggesting the importance of the extracellular matrix (ECM) in sarcoma, 17 we investigated the expression patterns of extracellular matrix genes in EPS (Figure S6 ). Four ECM genes were significantly overexpressed in distal EPS ( COL4A1 , 3.3× overexpression, COL5A , 4.2× overexpression, COL12A1 , 2.5× overexpression, COLEC12 , 1.5× overexpression), but significance did not hold true under multiple comparison testing.…”

Section: Resultsmentioning

confidence: 99%

Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology

Rasmussen

Jin

Bickford

et al. 2022

Clinical & Translational Med

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Background Metastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat. Methods In order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next‐generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance. Results Other biologically inspired functional interrogations of EPS cultures using gene knockdown or chemical probes demonstrated only limited to modest efficacy in vitro. However, our molecular studies uncovered distinguishing features (including retained dysfunctional SMARCB1 expression and elevated GLI3, FYN and CXCL12 expression) of distal, paediatric/young adult‐associated EPS versus proximal, adult‐associated EPS. Conclusions Overall results highlight the complexity of the disease and a limited chemical space for therapeutic advancement. However, subtle differences between the two EPS subtypes highlight the biological disparities between younger and older EPS patients and emphasise the need to approach the two subtypes as molecularly and clinically distinct diseases.

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Defining the Extracellular Matrix of Rhabdomyosarcoma

Cited by 13 publications

References 34 publications

miR-139-5p Was Identified as Biomarker of Different Molecular Subtypes of Breast Carcinoma

miR-139-5p Was Identified as Biomarker of Different Molecular Subtypes of Breast Carcinoma

DWI and IVIM Imaging in a Murine Model of Rhabdomyosarcoma: Correlations with Quantitative Histopathologic Features

Functional genomic analysis of epithelioid sarcoma reveals distinct proximal and distal subtype biology

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