Tumor Microenvironment Introduction
- The tumor microenvironment consists of four components:
- Cancer cells
- Non-cancer cells
- Secreted soluble factors
- Non-cellular, solid material
- The actual composition of the tumor microenvironment is highly variable.
Conditions within the tumor microenvironment
- Low oxygen levels (hypoxia), acidic conditions (low pH), and low sugar (glucose) levels are common conditions in tumors.
- Conditions within the tumor microenvironment affect both cancer cells and normal cells.
- The tissue within and surrounding a tumor is often disorganized.
Inflammatory Cells in Cancer
- The immune system can inhibit or promote tumor growth.
- Many cancers are associated with chronic inflammatory conditions that activate cells of the innate immune system.
- Macrophages secrete factors that enhance tumor cell proliferation, invasion, and promote angiogenesis.
Fibroblasts in Cancer
- Fibroblasts are the predominant cells in the stroma.
- Changes in fibroblast behavior are associated with tumor progression.
- Matrix metalloproteinases (MMPs) produced by fibroblasts degrade the extracellular matrix.
- MMPs are key players in cancer initiation, metastasis, and angiogenesis.
The Tumor Stroma and Metastasis
- Seed and Soil hypothesis: given tumor cells (seeds) can only colonize particular distant tissues (soil) that have a suitable growth environment.
- Two key events must occur for site-specific metastasis to occur: 1) formation of a viable landing spot and 2) expression of appropriate genes in the tumor cells.
- Tumor cells may invade foreign tissue but fail to colonize it. The reasons for this are unknown. These cells are considered 'dormant' cancer cells.
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