Gastric carcinogenesis: a comprehensive review of the angiogenic pathways

Abstract

Gastric cancer (GC) is undoubtedly one of the most prevalent malignancies worldwide. Since GC is the second leading cause of cancer-related deaths with nearly one million new diagnoses reported every year, there is a need for the development of new, effective treatment strategies of GC. Gastric carcinogenesis is a complex process that is induced by numerous factors and further stimulated by many pro-oncogenic pathways. Angiogenesis is the process of the new blood vessels formation from the already existing ones and it significantly contributes to the progression of gastric tumorigenesis and the growth of the cancerous tissues. The newly formed vessels provide cancer cells with proper nutrition, growth factors, and oxygen supply that are crucial for tumor growth and progression. Tumor-associated vessels differ from the physiological ones both morphologically and functionally. They are usually inefficient and unevenly distributed due to structural transformations. Thus, the development of the angiogenesis inhibitors that possess therapeutic effects has been the main focus of recent studies. Angiogenesis inhibitors mostly affect the vascular endothelial growth factor (VEGF) pathway since it is a major factor that stimulates the pro-angiogenic pathways. The aim of this review was to describe and summarize other promising molecular pathways that might be crucial in further improvements in GC therapies. This article provides an overview of how a meaningful role in tumor progression the angiogenetic process has. Furthermore, this review includes a description of the most important angiogenic factors as well as pathways and their involvement in gastric carcinogenesis.

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches

“…The above-mentioned process is due to the switch of the type 1 cadherin (E-cadherin) into the neural cadherin (N-cadherin) that is promoted by the deregulations in the epithelial gene expression and activation of the genes responsible for the induction of the mesenchymal phenotype [ 26 ]. Besides, crucial events of EMT also include the loss of cellular polarity and reorganization of the cellular cytoskeleton structure; EMT also facilitates the induction of angiogenesis [ 27 , 28 ]. Cells that have undergone the EMT process are resistant to apoptosis and present enhanced motility [ 29 ].…”

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Gastric Cancer

“…Interactively, CAFs are capable of synergistically initiating and enhancing EMT (Bhowmick et al, 2004;Lee et al, 2006;Thiery and Sleeman, 2006;Ham et al, 2019); CAFs could also regulate and maintain the stemness of gastric cancer cells via TGFβ signaling (Hasegawa et al, 2014). Pathological angiogenesis has been widely described as a crucial process enabling the expansion of cancerous tissues, as well as the invasion and metastasis of GC cells (Chen et al, 2004;Hoff and Machado, 2012;Forma et al, 2021). CAFs contributed dominantly to the uncontrolled angiogenesis by inducing a hypoxia TME (Kugeratski et al, 2019) and producing proangiogenic factors like galectin-1 (Tang et al, 2016), vascular endothelial growth factor (VEGF) (De Francesco et al, 2013), and hepatocyte growth factor (HGF) (Ding et al, 2018).…”

Histomorphological Characteristics and Pathological Types of Hyperproliferation of Gastric Surface Epithelial Cells

“…Therefore, further investigation of tumor vessel formation and its mechanisms contributes to the development of new strategies to treat cancer. Vascular endothelial growth factors (VEGFs) family, epidermal growth factor (EGF) family, resistin-like molecule-α (RELM-α), platelet-derived growth factor-β, hypoxiainducible factors, and microRNAs (miRNAs) are accepted to be involved in the induction and progression of angiogenesis [26]. microRNAs (miRNAs) (e.g., miR-135a; miR-377; miR-218, miR-130, miR-495) are accepted to be critical regulators of tumor angiogenesis and received focus as promising targets in new antiangiogenic therapies [14].…”