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Cancer Biology & Therapy Dec 2023Vascular endothelial growth factor (VEGF) plays key roles in angiogenesis, vasculogenesis, and wound healing. In cancers, including triple negative breast cancer (TNBC),...
Vascular endothelial growth factor (VEGF) plays key roles in angiogenesis, vasculogenesis, and wound healing. In cancers, including triple negative breast cancer (TNBC), VEGF has been associated with increased invasion and metastasis, processes that require cancer cells to traverse through the extracellular matrix (ECM) and establish angiogenesis at distant sites. To further understand the role of VEGF in modifying the ECM, we characterized VEGF-mediated changes in the ECM of tumors derived from TNBC MDA-MB-231 cells engineered to overexpress VEGF. We established that increased VEGF expression by these cells resulted in tumors with reduced collagen 1 (Col1) fibers, fibronectin, and hyaluronan. Molecular characterization of tumors identified an increase of MMP1, uPAR, and LOX, and a decrease of MMP2, and ADAMTS1. α-SMA, a marker of cancer associated fibroblasts (CAFs), increased, and FAP-α, a marker of a subset of CAFs associated with immune suppression, decreased with VEGF overexpression. Analysis of human data from The Cancer Genome Atlas Program confirmed mRNA differences for several molecules when comparing TNBC with high and low VEGF expression. We additionally characterized enzymatic changes induced by VEGF overexpression in three different cancer cell lines that clearly identified autocrine-mediated changes, specifically uPAR, in these enzymes. Unlike the increase of Col1 fibers and fibronectin mediated by VEGF during wound healing, in the TNBC model, VEGF significantly reduced key protein components of the ECM. These results further expand our understanding of the role of VEGF in cancer progression and identify potential ECM-related targets to disrupt this progression.
Topics: Humans; Autocrine Communication; Extracellular Matrix; Fibronectins; Triple Negative Breast Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 37389973
DOI: 10.1080/15384047.2023.2184145 -
Biomedicine & Pharmacotherapy =... Jul 2023Cardiac hypertrophy is characterized by cardiac structural remodeling, fibrosis, microvascular rarefaction, and chronic inflammation. The heart is structurally organized... (Review)
Review
Cardiac hypertrophy is characterized by cardiac structural remodeling, fibrosis, microvascular rarefaction, and chronic inflammation. The heart is structurally organized by different cell types, including cardiomyocytes, fibroblasts, endothelial cells, and immune cells. These cells highly interact with each other by a number of paracrine or autocrine factors. Cell-cell communication is indispensable for cardiac development, but also plays a vital role in regulating cardiac response to damage. Although cardiomyocytes and fibroblasts are deemed as key regulators of hypertrophic stimulation, other cells, including endothelial cells, also exert important effects on cardiac hypertrophy. More particularly, endothelial cells are the most abundant cells in the heart, which make up the basic structure of blood vessels and are widespread around other cells in the heart, implicating the great and inbuilt advantage of intercellular crosstalk. Cardiac microvascular plexuses are essential for transport of liquids, nutrients, molecules and cells within the heart. Meanwhile, endothelial cell-mediated paracrine signals have multiple positive or negative influences on cardiac hypertrophy. However, a comprehensive discussion of these influences and consequences is required. This review aims to summarize the basic function of endothelial cells in angiogenesis, with an emphasis on angiogenic molecules under hypertrophic conditions. The secondary objective of the research is to fully discuss the key molecules involved in the intercellular crosstalk and the endothelial cell-mediated protective or detrimental effects on other cardiac cells. This review provides a more comprehensive understanding of the overall role of endothelial cells in cardiac hypertrophy and guides the therapeutic approaches and drug development of cardiac hypertrophy.
Topics: Humans; Endothelial Cells; Cardiomegaly; Myocytes, Cardiac; Paracrine Communication; Fibroblasts
PubMed: 37121147
DOI: 10.1016/j.biopha.2023.114799