Abstract
Tumor angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interactions contribute functionally to tumor growth and metastasis. Activated fibroblasts and macrophages in tumor stroma play important roles in angiogenesis and tumor progression. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, platelet-derived endothelial cell growth factor, and angiopoietin. In addition, Helicobacter pylori infection increases tumor cell expression of metastasis-related genes including those encoding several angiogenic factors. We review the current understanding of molecular mechanisms involved in angiogenesis and lymphangiogenesis of human gastric cancer.
Highlights
Gastric cancer is the world’s second leading cause of cancer death [1]
These findings suggest that vascular endothelial growth factor (VEGF)-A promotes angiogenesis and progression of human gastric cancers, especially those of the intestinal-type
These results suggest that VEGF-C is a dominant regulator of lymphangiogenesis in early-stage human gastric cancer
Summary
Gastric cancer is the world’s second leading cause of cancer death [1]. Tumor tissue, including gastric cancer, consists of both tumor cells and stromal cells. Tumor growth and metastasis are determined by tumor cells themselves and by stromal cells. Recent studies have shown that interactions between tumor cells and activated stromal cells create a unique microenvironment that is crucial for tumor growth and metastasis (Figure 1) [3, 4]. The organspecific microenvironment can influence the growth, vascularization, invasion, and metastasis of human neoplasms [5]. The growth of lymphatic vessels (lymphangiogenesis) in the tumor periphery correlates with lymphatic metastasis in cases of gastric cancer [13, 14]. We discuss the role of angiogenic and lymphangiogenic fact-ors in the growth and metastasis of human gastric cancer
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