Gastric carcinogenesis: a comprehensive review of the angiogenic pathways
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CLINICAL REVIEW
Gastric carcinogenesis: a comprehensive review of the angiogenic pathways Alicja Forma1 · Magdalena Tyczyńska2 · Paweł Kędzierawski1 · Klaudyna Gietka1 · Monika Sitarz3 Received: 15 September 2020 / Accepted: 31 October 2020 © The Author(s) 2020
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. Keywords Gastric cancer · Carcinogenesis · Tumorigenesis · Angiogenesis · Pro-angiogenic pathways Abbreviations AFP α-Fetoprotein Angs Angiopoietins
* Alicja Forma [email protected] Magdalena Tyczyńska [email protected] Paweł Kędzierawski [email protected] Klaudyna Gietka [email protected] Monika Sitarz [email protected] 1
Department of Forensic Medicine, Medical University of Lublin, 20‑090 Lublin, Poland
2
Department of Human Anatomy, Medical University of Lublin, 20‑090 Lublin, Poland
3
Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20‑090 Lublin, Poland
CEACAM6 Carcinoembryonic antigen-related cell adhesion molecule 6 COX-2 Cyclooxygenase-2 CRYAB Alpha-B crystallin CXCR4 C-X-C motif chemokine receptor 4 CXCR7 C-X-C motif chemokine receptor 7 ECs Endothelial cells EGF Epidermal growth factor EMT Epithelial–mesenchymal transition FGFs Fibroblast growth factors Fox Mammalian forkhead box FOXO1 Forkhead box O1 GC Gastric cancer HIF-1 and HIF-2 Hypoxia-inducible factor 1 and 2 HMGB1 High-mobility grou
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