Module 2: Understanding Cancer Metastasis
A deep dive into the complex process of cancer metastasis, from molecular mechanisms to clinical applications and therapeutic strategies.
The Tumor Microenvironment: A Complex Cellular Ecosystem
Tumors don't exist in isolation - they're surrounded by a diverse community of cells that can either support or inhibit cancer progression.
Key Insights
Tumors contain many cell types beyond cancer cells
Communication between cells drives tumor progression
Microenvironment influences growth and metastasis
Understanding this ecosystem reveals therapeutic targets
Components of the Tumor Microenvironment
Each cell type plays a unique role in tumor progression
Cancer Cells
Role: Primary drivers of tumor growth, invasion, and metastasis
Key Characteristics:
• Abnormal proliferation
• Resistance to cell death
• Invasive capabilities
• Metabolic reprogramming
Normal Cells
Role: Can be co-opted to support tumor growth or may resist cancer progression
Key Characteristics:
• Maintain normal functions
• May be influenced by cancer signals
• Can provide structural support
• May compete for resources
Blood Vessels & Blood Cells
Role: Essential for tumor growth beyond 2-3mm and metastatic spread
Key Characteristics:
• Often structurally abnormal
• Increased permeability
• Provide metastatic pathways
• Deliver immune cells
Extracellular Matrix (ECM)
Role: Acts as barrier to invasion but can be remodeled by cancer cells
Key Characteristics:
• Composed of collagen, fibronectin, laminin
• Provides tissue structure
• Barrier to cancer cell invasion
• Can be degraded by matrix metalloproteinases
Neurons
Role: Can promote tumor growth through neurotransmitters and provide invasion routes
Key Characteristics:
• Secrete neurotransmitters and peptides
• Some molecules promote tumor growth
• Can serve as invasion highways
• Present in most tissues
Fibroblasts & CAFs
Role: Cancer-Associated Fibroblasts (CAFs) actively promote tumor progression
Key Characteristics:
• Produce collagen and other fibers
• CAFs secrete growth factors
• Promote EMT and invasion
• Support angiogenesis
Adipose Tissue
Role: White adipose tissue (WAT) can promote tumor formation and progression
Key Characteristics:
• Linked to increased cancer risk
• Secretes pro-tumorigenic proteins
• Promotes EMT and invasion
• Associated with obesity
Immune Cells
Role: Can either eliminate cancer cells or be co-opted to support tumor growth
Key Characteristics:
• Include T cells, B cells, macrophages
• Some kill abnormal cancer cells
• Others suppress immune responses
• Can travel with metastatic cells
Macrophage Polarization: A Key Example
Macrophages demonstrate the complexity of immune cell roles in cancer
M1 Macrophages
Anti-cancer- Pro-inflammatory
- Stimulate immune responses
- Promote cancer cell death
- Respond to infection/stress
M2 Macrophages
Pro-cancer- Immunosuppressive
- Pro-angiogenic
- Favor tumor growth
- Suppress other immune cells
Secreted Molecules: Chemical Communication
Cells communicate through various secreted factors that influence tumor behavior
Growth Factors
Promote cell division and angiogenesis
Cytokines
Regulate immune responses
Chemokines
Direct cell migration and invasion
Matrix Metalloproteinases
Degrade ECM to enable invasion
Clinical Implications
Understanding the tumor microenvironment has revolutionized cancer treatment approaches. Rather than targeting cancer cells alone, modern therapies increasingly focus on disrupting the supportive ecosystem that enables tumor growth and metastasis.
Therapeutic Insight: The tumor microenvironment represents a rich source of therapeutic targets, from anti-angiogenic drugs to immunotherapies that reprogram the immune landscape.