Module 2: Understanding Cancer Metastasis • Topic 5 of 13
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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

VEGFPDGFTGF-β

Cytokines

Regulate immune responses

IL-6TNF-αInterferons

Chemokines

Direct cell migration and invasion

CXCL12CCL2

Matrix Metalloproteinases

Degrade ECM to enable invasion

MMP-2MMP-9

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.