Supplementary Figure 5 from CSPG4 as a Target of Antibody-Based Immunotherapy for Malignant Mesothelioma

PDF file, 3582K, CSPG4-specific mAb TP41.2 reduces MM wound healing.</p

Supplementary Figure Legend from CSPG4 as a Target of Antibody-Based Immunotherapy for Malignant Mesothelioma

PDF file, 91K.</p

Supplementary Figure 3 from CSPG4 as a Target of Antibody-Based Immunotherapy for Malignant Mesothelioma

PDF file, 4250K, The interaction between CSPG4 and the extracellular matrix (ECM) promotes MM cell adhesion.</p

Supplementary Figure 4 from CSPG4 as a Target of Antibody-Based Immunotherapy for Malignant Mesothelioma

PDF file, 2167K, CSPG4 knockdown reduces MM cell migration.</p

Supplementary Figure 1 from CSPG4 as a Target of Antibody-Based Immunotherapy for Malignant Mesothelioma

PDF file, 1296K, Characterization of CSPG4 in Malignant Mesothelioma.</p

Supplementary Figure 2 from CSPG4 as a Target of Antibody-Based Immunotherapy for Malignant Mesothelioma

PDF file, 2191K, Silencing of CSPG4 expression in MM cells.</p

Supplementary Figure 6 from CSPG4 as a Target of Antibody-Based Immunotherapy for Malignant Mesothelioma

PDF file, 2458K, CSPG4 knockdown decreases the rate of wound healing in MM cells.</p

DataSheet_1_The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling.pdf

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited therapeutic options. The extracellular matrix protein fibulin-3/EFEMP1 accumulates in the pleural effusions of MPM patients and has been proposed as a prognostic biomarker of these tumors. However, it is entirely unknown whether fibulin-3 plays a functional role on MPM growth and progression. Here, we demonstrate that fibulin-3 is upregulated in MPM tissue, promotes the malignant behavior of MPM cells, and can be targeted to reduce tumor progression. Overexpression of fibulin-3 increased the viability, clonogenic capacity and invasion of mesothelial cells, whereas fibulin-3 knockdown decreased these phenotypic traits as well as chemoresistance in MPM cells. At the molecular level, fibulin-3 activated PI3K/Akt signaling and increased the expression of a PI3K-dependent gene signature associated with cell adhesion, motility, and invasion. These pro-tumoral effects of fibulin-3 on MPM cells were disrupted by PI3K inhibition as well as by a novel, function-blocking, anti-fibulin-3 chimeric antibody. Anti-fibulin-3 antibody therapy tested in two orthotopic models of MPM inhibited fibulin-3 signaling, resulting in decreased tumor cell proliferation, reduced tumor growth, and extended animal survival. Taken together, these results demonstrate for the first time that fibulin-3 is not only a prognostic factor of MPM but also a relevant molecular target in these tumors. Further development of anti-fibulin-3 approaches are proposed to increase early detection and therapeutic impact against MPM.</p

DataSheet_2_The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling.pdf

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited therapeutic options. The extracellular matrix protein fibulin-3/EFEMP1 accumulates in the pleural effusions of MPM patients and has been proposed as a prognostic biomarker of these tumors. However, it is entirely unknown whether fibulin-3 plays a functional role on MPM growth and progression. Here, we demonstrate that fibulin-3 is upregulated in MPM tissue, promotes the malignant behavior of MPM cells, and can be targeted to reduce tumor progression. Overexpression of fibulin-3 increased the viability, clonogenic capacity and invasion of mesothelial cells, whereas fibulin-3 knockdown decreased these phenotypic traits as well as chemoresistance in MPM cells. At the molecular level, fibulin-3 activated PI3K/Akt signaling and increased the expression of a PI3K-dependent gene signature associated with cell adhesion, motility, and invasion. These pro-tumoral effects of fibulin-3 on MPM cells were disrupted by PI3K inhibition as well as by a novel, function-blocking, anti-fibulin-3 chimeric antibody. Anti-fibulin-3 antibody therapy tested in two orthotopic models of MPM inhibited fibulin-3 signaling, resulting in decreased tumor cell proliferation, reduced tumor growth, and extended animal survival. Taken together, these results demonstrate for the first time that fibulin-3 is not only a prognostic factor of MPM but also a relevant molecular target in these tumors. Further development of anti-fibulin-3 approaches are proposed to increase early detection and therapeutic impact against MPM.</p

Supplementary Figure 1 from HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients

Comparison of mesothelin and HMGB1 levels using respectively different reagents or techniques</p