Cancer Metastasis Mechanisms and Stages

Cancer Metastasis: Steps and Mechanisms

• Human cancers progress through a series of steps forming primary tumors, then potentially metastasizing.
• Factors like fast food, processed meat, and tobacco use accelerate mutation development, impacting cancer progression, including lung cancer.
• Primary tumors can become metastatic, posing a greater threat than local cancer.

Development of Metastatic Cancer

• Circulating Tumor Cells (CTCs) are shed from primary tumors into the bloodstream.
• A minuscule fraction (less than 0.01%) of these cells become metastatic.
• Metastatic cells must meet specific requirements:

Metastatic Cell Requirements

• Leaving the Primary Tumor:

  • Proteinases degrade basement membrane and extracellular matrix (ECM), enabling escape.
  • Key enzymes involved: Type IV Collagenase and Cathepsin B.

• Entering the Circulation:

  • Angiogenesis and lymphogenesis establish pathways for cancer cell entry.
  • Cancer cells separate, exhibit motility to move towards blood/lymph vessels.

• Surviving in the Circulation:

  • Platelets coat cancer cells, protecting them from immune response and stress.
  • Selectin-mediated binding of platelets creates a protective layer.

• Overcoming Host Defenses:

  • Low immunogenicity and immune suppression are common.

• Extravasation (Exiting Blood Vessels):

  • Cancer cells navigate non-porous blood vessels at distant sites.
  • Motility, flexibility, and activation of specific genes needed.
  • ECM & basement membrane degradation facilitates invasion of new tissues.

• Establishing a Metastatic Colony:

  • Cancer cells adapt to new tissue environments; establish colonies.
  • The Seed-Soil Hypothesis describes the need for compatible tissue environments.

Seed-Soil Hypothesis

• A tumor's metastatic potential depends on interactions with tissues promoting growth and survival.
• Specific tissues are "best soil" for particular cancers (e.g., prostate cancer to bone).
• Cancer cells select the optimal environment for growth, similar to seeds choosing favorable soil.

EMT and MET: Cellular Transformation

• Cancer cells employ normal biological processes, such as the epithelial-mesenchymal transition (EMT), for metastasis.

• EMT (embryonic process) allows cells to transition from non-motile, structured epithelium to motile, flexible mesenchyme.

• In Cancer: Epithelial cancer cells, undergoing EMT, reduce epithelial markers and gain mesenchymal properties.

• This enables invasion, entry into circulation, and survival.

• Mesenchymal cells are adapted for motility, invasion, and circulation.

• Cells re-establish the epithelial structure (MET) at the secondary site, forming new tumors.

• Metastatic process largely driven by epigenetic modifications.

• Key transcription factors (TFs), activated by pathways like Hedgehog (Hh) and Wnt—critical in embryonic development—are frequently involved in cancers.

• Initial mutations in regulatory genes (e.g., APC) can drive cancers into EMT-related pathways.

This quiz explores the intricate processes involved in cancer metastasis, highlighting the steps from primary tumors to metastatic cells. Learn about the factors that influence cancer progression and the specific requirements that metastatic cells must meet to spread throughout the body. Test your knowledge on this critical aspect of cancer biology.