Journal
CANCER SCIENCE
Volume 111, Issue 8, Pages 2696-2707Publisher
WILEY
DOI: 10.1111/cas.14521
Keywords
CAFs; endothelial cells; gastric cancer; gastrin; TAMs
Categories
Funding
- Inoue Science Research Award
- Advanced Research and Development Programs for Medical Innovation (PRIME)
- Kanae Foundation of the Promotion of Medical Science
- KAKENHI [17K09347, 17H05081]
- Princess Takamatsu Cancer Research Fund
- Yokoyama Clinical Pharmacological Research Foundation
- SENSHIN Medical Research Foundation
- Kowa Life Science Foundation
- Takeda Science Foundation
- Bristol Myers Squibb
- Pharmacological Research Foundation
- Japan Agency for Medical Research and Development
- Grants-in-Aid for Scientific Research [17K09347, 17H05081] Funding Source: KAKEN
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The tumor microenvironment favors the growth and expansion of cancer cells. Many cell types are involved in the tumor microenvironment such as inflammatory cells, fibroblasts, nerves, and vascular endothelial cells. These stromal cells contribute to tumor growth by releasing various molecules to either directly activate the growth signaling in cancer cells or remodel surrounding areas. This review introduces recent advances in findings on the interactions within the tumor microenvironment such as in cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells, in particular those established in mouse gastric cancer models. In mice, myofibroblasts in the gastric stroma secrete R-spondin and support normal gastric stem cells. Most CAFs promote tumor growth in a paracrine manner, but CAF population appears to be heterogeneous in terms of their function and origin, and include both tumor-promoting and tumor-restraining populations. Among immune cell populations, tumor-associated macrophages, including M1 and M2 macrophages, and myeloid-derived suppressor cells (MDSCs), are reported to directly or indirectly promote gastric tumorigenesis by secreting soluble factors or modulating immune responses. Endothelial cells or blood vessels not only fuel tumors with nutrients, but also interact with cancer stem cells and immune cells by secreting chemokines or cytokines, and act as a cancer niche. Understanding these interactions within the tumor microenvironment would contribute to unraveling new therapeutic targets.
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