Molecular Expression of bone marrow angiogenic factors, cell-cell adhesion molecules and matrix-metallo-proteinase plasma cellular disorders: a molecular panel to investigate disease progression

Abstract

Increasing levels of angiogenesis play an important role in the pathogenesis and progression of multiple myeloma (MM). Malignant plasma cells promote a gradual increase in the degree of angiogenesis, modulation of specific cell-cell adhesion molecules and secretion of matrix-metallo-proteinases (MMPs), changing the BM composition from benign conditions, such as MGUS, to smouldering multiple myeloma (SM) and to active MM. We aimed to identify a gene expression profile, helpful to discriminate the “angiogenic potential” in BM and PB plasma cells from MGUS, SMM and active MM patients analyzed at diagnosis. We analyzed the expression of cell-cell adhesion molecules such as VE-Cadherin, E-Cadherin MCAM/MUC18/CD146 and of the MMP-2 and MMP-9. MCAM/MUC18 expression resulted mostly associated with that of the pivotal angiogenic factors VEGF and Ang2, and in MGUS the pattern was different in steady state, compared to progression towards SM. Furthermore, E-Cadherin, the main epithelial cell-cell-adhesion molecule, unexpectedly resulted overexpressed in MM.
 

Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients

“…The selected gene-expression panel, with the exception of melanoma tissue stem and differentiation markers TyrOH, MelanA/MART1, and ABCB5, was previously tested and validated on 14 primary tumor cell lines including LnCap, DU145 (prostate cancer); MB 231, MCF7 (breast cancer); C33A, HeLa (cervix cancer); Mel 10, Mel 14, FO 1, Colo 38 (MM); SH-Sy5 (neuroblastoma); U87 (glioma); U266, Arp 1 (multiple myeloma), as partially reported in Table 2 (Rapanotti et al, 2018). The melanoma tissue stem and differentiation markers TyrOH, MelanA/MART1 were tested on Mel 10, Mel 14, FO 1, Colo 38 (MM), as previously reported (Rapanotti et al, 2009(Rapanotti et al, , 2014.…”

“…Performing one-step or nested PCR, we brought the sensitivity down even before 1 or 10 single melanoma cells (Rapanotti et al, 2009(Rapanotti et al, , 2014. The expression of proangiogenic, cell-cell adhesion factors and matrix metalloproteinases (VEGF, bFGF,VE-Cadh, E-CADH N-Cadh, MCAM/MUC18/CD146, MMP-2, and MMP-9) was heterogeneous (Rapanotti et al, 2018; Table 2). Nevertheless, all four melanoma cell lines (M10, M14, FO1, and Colo38) expressed all aforementioned genes and the melanoma tissue stem and differentiation markers TyrOH, MelanA/MART1, and ABCB5.…”

MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy

“…A qualitative expression panel of melanoma aggression markers, contemplating the angiogenic-potential, melanoma-initiating, and melanoma-differentiation drivers, as well as cell-cell adhesion molecules and matrix metalloproteinases, was characterized at the mRNA level [68,69].…”

“…So, all 60 cellular subsets were molecularly characterized by analyzing the following proangiogenic factors: vascular endothelial growth factor (VEGF); basic fibroblast growth factors (bFGF); cell-cell adhesion factors such as neuronal cadherin, (N-Cadh CDH2) and vascular endothelial cadherin (VE-Cadh CDH5); endothelial antigen CD146 isoforms (long, short, and 5 -portion); and matrix metalloproteinases (MMP-2, MMP-9) [68,69]. In this enlarged study, we also enrolled patients if staged AJCC ≥ pT1b with a confirmed diagnosis of histological and immune-histochemical malignant melanoma.…”

The role of bone marrow microenvironment in the progression of multiple myeloma from monoclonal gammopathy of undetermined significance

“…Диагностика и лечение множественной миеломы (HGF), FGF) и антиангиогенных факторов способст вует переходу MGUS в ММ [34,35].…”