0000000000133576
AUTHOR
Matteo Milani
showing 14 related works from this author
Additional file 1 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 1. Supplementary file 1. Supplementary Material & methods.
Additional file 6 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 6: Supplementary Figure S3. Immunohistochemistry staining of OPN IHC for OPN was performed in Fas lpr/lpr and OPN-/-Fas lpr/lpr mice with either no lymphoma or with lymphomatous cells. As expected, no staining is detected in case of OPN-deficient mice.
Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2022
Abstract Background Autoimmune disorders, including Systemic Lupus Erythematosus (SLE), are associated with increased incidence of hematological malignancies. The matricellular protein osteopontin (OPN) has been linked to SLE pathogenesis, as SLE patients show increased serum levels of OPN and often polymorphisms in its gene. Although widely studied for its pro-tumorigenic role in different solid tumours, the role of OPN in autoimmunity-driven lymphomagenesis has not been investigated yet. Methods To test the role of OPN in the SLE-associated lymphomagenesis, the SLE-like prone Faslpr/lpr mutation was transferred onto an OPN-deficient background. Spleen from Faslpr/lpr and OPN-/-Faslpr/lpr …
WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer
2019
Triple-negative breast cancers (TNBCs) are characterized by a poor prognosis and lack of targeted treatments, and thus, new therapeutic strategies are urgently needed. Inhibitors against programmed death-1 (PD-1)/PD-1 ligand (PD-L1) have shown significant efficacy in various solid cancers, but their activity against TNBCs remains limited. Here, we report that human TNBCs molecularly stratified for high levels of PD-L1 (PD-L1High) showed significantly enriched expression of immune and cancer stemness pathways compared with those with low PD-L1 expression (PD-L1Low). In addition, the PD-L1High cases were significantly associated with a high stemness score (SSHigh) signature. TNBC cell lines g…
Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer.
2021
Abstract Fatal neuroendocrine differentiation (NED) of castration-resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients. The design of effective therapies for neuroendocrine prostate cancer (NEPC) is complicated by limited knowledge of the molecular mechanisms governing NED. The paucity of acquired genomic alterations and the deregulation of epigenetic and transcription factors suggest a potential contribution from the microenvironment. In this context, whether ADT/ARPI induces stromal cells to release NED-promoting molecules and the underlying molecular networks are unestablis…
SPARC regulation of PMN clearance protects from pristane-induced lupus and rheumatoid arthritis
2021
Summary The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in myeloid cells. We investigated the role of SPARC in autoimmunity using the pristane-induced model of lupus that, in mice, mimics human systemic lupus erythematosus (SLE). Sparc−/− mice developed earlier and more severe renal disease, multi-organ parenchymal damage, and arthritis than the wild-type counterpart. Sparc+/- heterozygous mice showed an intermediate phenotype suggesting Sparc gene dosage in autoimmune-related events. Mechanistically, reduced Sparc expression in neutrophils blocks their clearance by macrophages, through defective delivery of don'…
Transcriptional Profiles and Stromal Changes Reveal Bone Marrow Adaptation to Early Breast Cancer in Association with Deregulated Circulating microRN…
2020
Abstract The presence of a growing tumor establishes a chronic state of inflammation that acts locally and systemically. Bone marrow responds to stress signals by expanding myeloid cells endowed with immunosuppressive functions, further fostering tumor growth and dissemination. How early in transformation the cross-talk with the bone marrow begins and becomes detectable in blood is unknown. Here, gene expression profiling of the bone marrow along disease progression in a spontaneous model of mammary carcinogenesis demonstrates that transcriptional modifications in the hematopoietic compartment occurred as early as preinvasive disease stages. The transcriptional profile showed downregulation…
SPARC regulation of PMN clearance protects from pristane induced lupus and rheumatoid arthritis
2020
AbstractOne step along the pathogenesis of Systemic lupus erythematosus (SLE) is associated with polymorphonuclear leukocyte (PMN) death and their ineffective removal by M2-macrophages. The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in M2-macrophages and myeloid cells. To investigate the role of SPARC in autoimmunity, we adopted a pristane–induced model of lupus in mice, which recapitulates clinical manifestations of human SLE. Sparc-/- mice developed earlier and more severe renal disease, lung and liver parenchymal damage than the WT counterpart. Most prominently, Sparc-/- mice had anticipated and severe occurr…
Additional file 4 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 4: Supplementary Figure S1. Evaluation of autoimmunity in Faslpr/lpr and OPN-/-Faslpr/lpr mice. A. Quantification of OPN in sera from Faslpr/lpr mice at 2 (n=8) and 5 months of age (n=7) by ELISA. Sera from BALB/c and OPN-/- mice were tested as controls. Data are expressed as ng/ml and are a pool of 2 experiments (*, P<0.05; Ordinary one way ANOVA). B. Flow cytometry analysis showing the relative number of splenic autoimmune CD3+B220+ T cells in Faslpr/lpr (n=15) and OPN-/-Faslpr/lpr mice (n=18) and at about 5-6 months of age. The graph shows a pool of 3 different experiments (***, P<0.001; Student t test). C. Representative spleen photograph from BALB/c, OPN-/-, Faslp…
Additional file 7 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 7: Supplementary Figure S4. Characterization of OPL239 and OPL241 DLBCL cell lines. A. Flow cytometry analysis showing the expression of B220, IgM, IgD and IgA in OPL239 and OPL241 cell lines. B. Hardy’s multiparametric flow cytometry panel illustrating the expression of CD93, CD21/35 and CD23 on OPL239 and OPL241 cell lines. C. Flow cytometry analysis showing the expression of TLR9 on OPL239 and OPL241 cell lines. D. RT-PCR analysis showing Spp1 mRNA level in overexpressing cell variants. E. Western blot for OPN protein expression (in presence or not of BFA, that blocks protein secretion) in parental and IRES-Green-based cell variants. 4T1 mammary cell line was used as posi…
Additional file 5 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 5: Supplementary Figure S2. Evaluation of the different spenic B cell subsets. A. Example of Hardy’s gating strategy to discern the different CD93+ immature (Transitional T1, T2, T3) and CD93- mature [follicular B (FOB), marginal zone B (MZB) and CD21/35-CD23-] B cell subsets in the spleen from a BALB/c mouse. B. Flow cytometry analysis based on Hardy’s multiparametric panel illustrating the fraction of splenic CD23+ FOB, CD21/35+ MZB cells, and CD23-CD21/35- cells from the spleens of naive and autoimmune mice. 3 mice per group were used for the experiment. Data are referred to one representative experiment out of 3 (***, P<0.001; Two-way ANOVA) (****, P<0.0001; Two-wa…
Additional file 8 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 8: Supplementary Figure S5. Expression of OPN in human GCB- and ABC-DLBCL samples. Immunohistochemistry analysis for OPN was performed on six cases for GCB- and ABC-DLBCLs. Representative images for two cases for each subtype are shown (quantification is shown in Figure 7B). Magnification 20X.
Additional file 2 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 2: Supplementary Table S1. Differentially expressed genes between CD19+ cellsfrom OPN-/-Fas lpr/lpr and Faslpr/lpr mice.
Additional file 3 of Intracellular osteopontin protects from autoimmunity-driven lymphoma development inhibiting TLR9-MYD88-STAT3 signaling
2023
Additional file 3: Supplementary Table S2. Differentially expressed genes between CD19+ cellsfrom OPN-/-and OPN+/+ mice.