Vascular Endothelial Growth Factor Ligands and Receptors in Breast Cancer

Abstract

Breast cancer (BC) is the most common malignancy responsible for the largest number of deaths in women worldwide. The risk of developing BC is predisposed by many factors such as age, presence of genetic mutations or body weight. The diagnosis is mostly made relatively late, which is why patients are exposed to radical surgical treatments, long-term chemotherapy and lower survival rates. There are no sufficiently sensitive and specific screening tests; therefore, researchers are still looking for new diagnostic biomarkers that would indicate the appearance of neoplastic changes in the initial stage of neoplasm. The VEGF family of proteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D, EG-VEGF, PlGF) and their receptors are significant factors in the pathogenesis of BC. They play a significant role in the process of angiogenesis and lymphangiogenesis in both physiological and pathological conditions. The usefulness of these proteins as potential diagnostic biomarkers has been initially proven. Moreover, the blockage of VEGF-related pathways seems to be a valid therapeutic target. Recent studies have tried to describe novel strategies, including targeting pericytes, use of miRNAs and extracellular tumor-associated vesicles, immunotherapeutic drugs and nanotechnology. This indicates their possible contribution to the formation of breast cancer and their usefulness as potential biomarkers and therapeutic targets.

A Preliminary Evaluation of Advanced Oxidation Protein Products (AOPPs) as a Potential Approach to Evaluating Prognosis in Early-Stage Breast Cancer Patients and Its Implication in Tumour Angiogenesis: A 7-Year Single-Centre Study

“…The current study shows a positive correlation between pre-treatment AOPPs and VEGF-A, which could be evidence of a relationship between oxidative protein damage in breast cancer and excessive angiogenic process. The role of VEGF in pathological angiogenesis in malignant tumours is essential [ 60 ]. Interestingly, the current study shows that lower pre-treatment levels of sVEGFR1 and lower post-treatment levels of sVEGFR2 were related to elevated levels of post-treatment AOPPs.…”

Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer

“…Generally, our results showed that pro-tumorigenic cytokines were reduced in CIRP/PyMT mice when compared to PyMT mice at both early and late time points. Interestingly, an assessment of the cytokines produced by mammary glands with early lesions showed significantly lower levels of VEGF-A, whose role in angiogenesis in breast cancer is well established [75,76]. CIRP was also recently shown to negatively regulate angiogenesis in vivo [77].…”

“…IL-10 downregulates the expression of Th1-type cytokines and increases the immune tolerance of cancer in the tumor microenvironment [62][63][64], while IL-1β is associated with an increased risk for bone metastasis in human breast cancer [78]. LIF was shown to promote migration and metastasis in breast cancer through the AKT-mTOR pathway [54], and elevation of VEGF-A in breast cancer is typically associated with poor prognosis and higher rates of metastasis [75,76]. IL-6 is known to promote invasiveness through epithelial-to-mesenchymal transition and is associated with the formation and maintenance of breast cancer stem cells [67].…”

A Retrospective Exploratory Analysis for Serum Extracellular Vesicles Reveals APRIL (TNFSF13), CXCL13, and VEGF-A as Prognostic Biomarkers for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

“…In a state of hypoxia, VEGF-A is secreted by a variety of cells, including tumor cells, macrophages, platelets, dendritic cells, astrocytes, and osteoblasts [66]. VEGF-A is secreted into several isoforms with different biological properties through alternative splicing of mRNA, and the dominant isoform is VEGF165 [67]. In EVs studies, Ko and colleagues found that VEGF189 was preferentially enriched in small EVs that were secreted by cancer cells [32], and Feng and colleagues identified a unique 90 kDa form of VEGF on the surface of breast cancer cell-derived microvesicles [68].…”