Podcast
Questions and Answers
What is the primary function of matrix metalloproteinases (MMPs) in cancer cell invasion?
What is the primary function of matrix metalloproteinases (MMPs) in cancer cell invasion?
Which protein family is primarily responsible for cell-cell adhesion in the context of cancer cell invasiveness?
Which protein family is primarily responsible for cell-cell adhesion in the context of cancer cell invasiveness?
What is a distinguishing feature of metastasis compared to simple invasiveness?
What is a distinguishing feature of metastasis compared to simple invasiveness?
Which of the following molecules plays a critical role in cell movement through the extracellular matrix?
Which of the following molecules plays a critical role in cell movement through the extracellular matrix?
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What cellular structure is primarily involved in the formation of lamellipodia during cancer cell invasion?
What cellular structure is primarily involved in the formation of lamellipodia during cancer cell invasion?
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Which of the following best describes the role of integrins in cancer cell behavior?
Which of the following best describes the role of integrins in cancer cell behavior?
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What is the primary consequence of E-cadherin loss in tumor cells?
What is the primary consequence of E-cadherin loss in tumor cells?
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Which Rho family GTPase is primarily responsible for the regulation of stress fiber formation?
Which Rho family GTPase is primarily responsible for the regulation of stress fiber formation?
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How do matrix metalloproteinases (MMPs) contribute to cancer metastasis?
How do matrix metalloproteinases (MMPs) contribute to cancer metastasis?
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In the context of the 'Seed & Soil' theory, what does the 'soil' represent?
In the context of the 'Seed & Soil' theory, what does the 'soil' represent?
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What is the role of TGF-beta in epithelial-mesenchymal transition (EMT)?
What is the role of TGF-beta in epithelial-mesenchymal transition (EMT)?
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Which of the following describes the main function of focal adhesions?
Which of the following describes the main function of focal adhesions?
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How does the activation of Src relate to integrin signaling?
How does the activation of Src relate to integrin signaling?
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What is the primary role of Cdc42 in cell migration?
What is the primary role of Cdc42 in cell migration?
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Which factor is essential for the activity of matrix metalloproteinases (MMPs)?
Which factor is essential for the activity of matrix metalloproteinases (MMPs)?
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Why is the study of cancer metastasis considered difficult?
Why is the study of cancer metastasis considered difficult?
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What is a significant characteristic of parenchymal tumor cells?
What is a significant characteristic of parenchymal tumor cells?
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Which of the following processes is directly associated with enhanced cell motility in tumor cells?
Which of the following processes is directly associated with enhanced cell motility in tumor cells?
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What role does the actin cytoskeleton play in normal cell migration?
What role does the actin cytoskeleton play in normal cell migration?
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Study Notes
Invasiveness vs. Metastasis
- Invasiveness is cancer cells invading surrounding tissues, while metastasis is the spread of cancer cells to distant organs, creating secondary tumors.
- For invasion and metastasis, cells need the ability to move through physical barriers (extracellular matrix - ECM).
- Proteins like integrins and cadherins, which are involved in cell-cell and cell-matrix adhesion, are often abnormally altered in cancers.
- Cancer cells produce more extracellular proteases (like matrix metalloproteinases - MMPs and plasminogen activator) than normal cells. These break down ECM, creating pathways.
- Intravasation is the process of cancer cells entering the blood or lymphatic vessels, a step in metastasis.
Cellular Systems in Normal and Tumor Cell Movement
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Adhesion Molecules:
- Integrins: Dimers that mediate cell-matrix interactions, anchoring to the ECM; altered profiles enhance cancer cell motility and survival.
- Cadherins: Maintain cell-cell adhesions; loss of E-cadherin promotes epithelial-mesenchymal transition (EMT) and invasion.
- Extracellular Matrix (ECM): The substrate for cell movement; degraded by MMPs in cancer to create invasive paths.
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Actin Cytoskeleton: Drives cell protrusion and contractility; dysregulated dynamics increase invasive behavior.
- Lamellipodia: Probe the environment, push the cell forward (Rac activation).
- Filopodia: Sense directional cues, guides migration (Cdc42 activation).
- Stress Fibers: Generate contractile force, support cell rear retraction(Rho activation).
- Focal Contacts/Focal Adhesions: Connect integrins to ECM and actin cytoskeleton.
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Rho Family GTPases: Molecular switches regulating actin cytoskeleton dynamics; aberrant activity promotes uncontrolled migration.
- Rac1: Promotes lamellipodia formation, actin polymerization at leading edge.
- RhoA: Regulates stress fiber formation and focal adhesion maturation, essential to rear contraction and cell polarity.
- Cdc42: Promotes filopodia formation, coordinates cell polarity.
Tumor Cell Types
- Parenchyma: The actual tumor cells.
- Stroma: The surrounding connective tissue support cells (fibroblasts), immune cells, and vasculature.
Integrin Signaling
- Integrin binding to ECM activates Focal Adhesion Kinase (FAK); FAK autophosphorylates, which activates signaling proteins.
- Src is used in integrin-mediated motility, activating several pathways.
- Grb2 leads to activation of the Ras/Raf/MEK/ERK (MAPK) pathway, affecting transcription.
- Ras can activate PI3K which promotes cell survival.
- Other small GTPases (Rac, Rho, Cdc42) are linked to cytoskeletal function, cell movement, and Raf activation.
MMPs and TIMPs
- Matrix Metalloproteinases (MMPs): A class of proteases that break down ECM proteins (require Zn++).
- MMP activity promotes invasion/metastasis; TIMPs (tissue inhibitors of MMPs) inhibit these processes.
- MMPs can free growth factors (e.g., VEGF) bound to ECM proteins, creating localized growth factor signaling.
"Seed & Soil" Theory
- Metastasis is a productive interaction between a cancer cell ("seed") and the tissues it spreads to ("soil").
- Successful metastasis depends on cells finding a new site with appropriate growth factors and ECM
- Those sites favor survival, proliferation, etc.
Epithelial-Mesenchymal Transition (EMT)
- EMT is the change from epithelial to mesenchymal cells.
- Features of EMT include: loss of epithelial markers (e.g., E-cadherin), gain of mesenchymal markers (e.g., N-cadherin, motility, invasiveness).
- Loss of E-cadherin and changes in B-catenin (a transcription factor) correlate with altered gene transcription for proliferation and differentiation.
- EMT promotes invasive and metastatic behavior.
Features Influencing Cancer Spread
- Cancer more often spreads along venous and drainage channels.
- Tumors near body cavities shed cancer cells into those cavities.
Studying Metastasis
- Difficulty in studying metastasis includes the need for appropriate experimental systems (e.g., successful in vivo metastasis is rare).
- Human tumor models in mice are limited because metastatic potential of human tumors in mice is often reduced and tumor growth and spread may differ from in humans.
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Description
Explore the critical differences between invasiveness and metastasis in cancer cells. Understand how proteins like integrins and cadherins influence cancer cell movement and the role of the extracellular matrix in these processes. This quiz will deepen your knowledge of tumor biology and cellular interactions.
