Cancer biology — Metastasis: Which of the following features contribute to metastatic spread of tumor cells (invasion through extracellular matrix and dissemination)?

Difficulty: Easy

Correct Answer: All of the above

Explanation:


Introduction / Context:
Metastasis is the multi-step process by which malignant cells escape the primary tumor, invade surrounding tissues, enter the circulation, and colonize distant organs. A key hallmark is the ability to breach the extracellular matrix and basement membranes using enzymes and altered regulatory pathways.



Given Data / Assumptions:

  • Tumor cells must detach, degrade matrix barriers, migrate, and survive in blood or lymph.
  • Matrix metalloproteinases (MMPs) and their regulators (TIMPs) control matrix degradation.
  • Question asks which listed factors are involved in metastasis.


Concept / Approach:
Invasion requires a protease-rich microenvironment. Overexpression of metalloproteinases and downregulation of their inhibitors promote matrix dissolution. Tumor cells also undergo epithelial–mesenchymal transition with enhanced motility and adhesion changes that synergize with proteolysis.



Step-by-Step Solution:

Identify the biological requirement: degrade extracellular matrix to invade.Link to enzymes: metalloproteinases cleave collagen, laminin, and other ECM components.Consider regulation: reduced TIMPs or other regulatory proteins amplifies MMP activity.Integrate the options: each listed factor facilitates ECM breakdown and invasion.


Verification / Alternative check:
Many metastatic tumors show a high MMP/TIMP ratio, correlating with invasive behavior and poor prognosis, confirming the functional importance of these changes.



Why Other Options Are Wrong:

  • Ability to dissolve ECM (alone): true but incomplete without regulation.
  • Increased metalloproteinases (alone): promotes invasion but not the whole picture.
  • Decreased regulators (alone): also favors invasion but is not sufficient by itself.


Common Pitfalls:
Assuming metastasis depends on a single gene or enzyme. In reality, it is a coordinated program involving proteases, adhesion changes, motility signaling, and survival pathways.



Final Answer:
All of the above

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