Surrounding Microenvironment

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Abeba Zewdu - One of the best experts on this subject based on the ideXlab platform.

  • mdm2 derived from dedifferentiated liposarcoma extracellular vesicles induces mmp2 production from preadipocytes
    Cancer Research, 2019
    Co-Authors: Lucia Casadei, Federica Calore, Danielle Braggio, Abeba Zewdu, Ameya Deshmukh, Paolo Fadda, Gonzalo Lopez
    Abstract:

    Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the MDM2 gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor Microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects. Overall, these findings indicate that MDM2 plays a crucial role in DDLPS by enabling cross-talk between tumor cells and the Surrounding Microenvironment and that targeting vesicular MDM2 could represent a therapeutic option for treating DDLPS. SIGNIFICANCE: Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by liposarcoma cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of proinflammatory cytokine IL6 from tumor-associated macrophages in a TLR7/8-dependent manner, which in turn promoted liposarcoma cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into liposarcoma progression, identifying communication between liposarcoma cells and their Microenvironment as a process critically involved in liposarcoma progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Cancer Res; 77(14); 3846-56. ©2017 AACR.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their Microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy.

Lucia Casadei - One of the best experts on this subject based on the ideXlab platform.

  • mdm2 derived from dedifferentiated liposarcoma extracellular vesicles induces mmp2 production from preadipocytes
    Cancer Research, 2019
    Co-Authors: Lucia Casadei, Federica Calore, Danielle Braggio, Abeba Zewdu, Ameya Deshmukh, Paolo Fadda, Gonzalo Lopez
    Abstract:

    Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the MDM2 gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor Microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects. Overall, these findings indicate that MDM2 plays a crucial role in DDLPS by enabling cross-talk between tumor cells and the Surrounding Microenvironment and that targeting vesicular MDM2 could represent a therapeutic option for treating DDLPS. SIGNIFICANCE: Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by liposarcoma cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of proinflammatory cytokine IL6 from tumor-associated macrophages in a TLR7/8-dependent manner, which in turn promoted liposarcoma cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into liposarcoma progression, identifying communication between liposarcoma cells and their Microenvironment as a process critically involved in liposarcoma progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Cancer Res; 77(14); 3846-56. ©2017 AACR.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their Microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy.

Kara Batte - One of the best experts on this subject based on the ideXlab platform.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by liposarcoma cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of proinflammatory cytokine IL6 from tumor-associated macrophages in a TLR7/8-dependent manner, which in turn promoted liposarcoma cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into liposarcoma progression, identifying communication between liposarcoma cells and their Microenvironment as a process critically involved in liposarcoma progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Cancer Res; 77(14); 3846-56. ©2017 AACR.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their Microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy.

Federica Calore - One of the best experts on this subject based on the ideXlab platform.

  • mdm2 derived from dedifferentiated liposarcoma extracellular vesicles induces mmp2 production from preadipocytes
    Cancer Research, 2019
    Co-Authors: Lucia Casadei, Federica Calore, Danielle Braggio, Abeba Zewdu, Ameya Deshmukh, Paolo Fadda, Gonzalo Lopez
    Abstract:

    Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the MDM2 gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor Microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects. Overall, these findings indicate that MDM2 plays a crucial role in DDLPS by enabling cross-talk between tumor cells and the Surrounding Microenvironment and that targeting vesicular MDM2 could represent a therapeutic option for treating DDLPS. SIGNIFICANCE: Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by liposarcoma cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of proinflammatory cytokine IL6 from tumor-associated macrophages in a TLR7/8-dependent manner, which in turn promoted liposarcoma cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into liposarcoma progression, identifying communication between liposarcoma cells and their Microenvironment as a process critically involved in liposarcoma progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy. Cancer Res; 77(14); 3846-56. ©2017 AACR.

  • exosome derived mir 25 3p and mir 92a 3p stimulate liposarcoma progression
    Cancer Research, 2017
    Co-Authors: Lucia Casadei, Federica Calore, Abeba Zewdu, Chad J Creighton, Michele Guescini, Kara Batte, Hans O Iwenofu
    Abstract:

    Despite the development of combined modality treatments against liposarcoma (LPS) in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by LPS cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of pro-inflammatory cytokine IL-6 from tumor-associated macrophages (TAM) in a TLR7/8-dependent manner, which in turn promoted LPS cell proliferation, invasion, and metastasis via this interaction with the Surrounding Microenvironment. Our findings provide novel and previously unreported insight into LPS progression, identifying communication between LPS cells and their Microenvironment as a process critically involved in LPS progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy.

Emanuel F Petricoin - One of the best experts on this subject based on the ideXlab platform.

  • development of a quantitative pd l1 assay using laser capture microdissection lcm based reverse phase protein microarray rppa workflow implications for precision medicine
    Journal of Clinical Oncology, 2018
    Co-Authors: Mariaelena Pierobon, Lance A Liotta, Elisa Baldelli, Alex K Hodge, Maria Isabella Sereni, Vienna Ludovini, Guido Bellezza, Lucio Crino, Emanuel F Petricoin
    Abstract:

    35Background: FDA approved IHC-based companion/complementary assays are routinely used to measure PD-L1 for treatment selection. However, IHC cut-point values vary across platforms and are based on subjective analysis that requires antigen retrieval methods. Even in highly selected populations of PD-L1 “positive” patients, clinical benefits are seen only in subgroups of patients. We tested the feasibility of utilizing LCM and RPPA as a new methodology for quantitative, operator independent measurements of PD-L1 on tumor cells. Methods: PD-L1 quantification by RPPA was compared to IHC on 23 lung cancers (LC). Tumor cells were isolated from the Surrounding Microenvironment using LCM. The E1L3N clone from Cell Signaling was used to quantify PD-L1 expression by RPPA and IHC. Reproducibility across antibody clones was then assessed on LCM procured tumor epithelia from 10 FFPE LC and 71 snap-frozen ovarian cancers (OC). PD-L1 measurements were compared between the Cell Signaling E1L3N and the Ventana SP-142 clo...

  • a pilot study exploring the molecular architecture of the tumor Microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray
    Molecular Oncology, 2016
    Co-Authors: Elisa Pin, Lance A Liotta, Elisa Baldelli, Alex K Hodge, Steven P Stratton, Claudio Belluco, Ray B Nagle, Jianghong Deng, Ting Dong, Emanuel F Petricoin
    Abstract:

    The cross-talk between tumor epithelium and Surrounding stromal/immune Microenvironment is essential to sustain tumor growth and progression and provides new opportunities for the development of targeted treatments focused on disrupting the tumor ecology. Identification of novel approaches to study these interactions is of primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based protein signaling activation mapping we explored the molecular interconnection between tumor epithelium and Surrounding stromal Microenvironment in 18 prostate cancer (PCa) specimens. Four specimen-matched cellular compartments (normal-appearing epithelium and its adjacent stroma, and malignant epithelium and its adjacent stroma) were isolated for each case. The signaling network analysis of the four compartments unraveled a number of molecular mechanisms underlying the communication between tumor cells and stroma in the context of the tumor Microenvironment. In particular, differential expression of inflammatory mediators like IL-8 and IL-10 by the stroma cells appeared to modulate specific cross-talks between the tumor cells and Surrounding Microenvironment.