Invasiveness vs. Metastasis in Cancer
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Questions and Answers

What is the difference between invasiveness and metastasis in cancer?

Invasiveness refers to the ability of cancer cells to penetrate surrounding tissues, while metastasis involves the spread of cancer cells from the primary tumor site to distant organs or tissues, forming secondary tumors.

What are the key cellular components involved in both normal and tumor cell movement?

The key components include adhesion molecules like integrins and cadherins, the extracellular matrix (ECM), the actin cytoskeleton, and signaling molecules like Rho GTPases.

What are the roles of integrins and cadherins in normal cell migration?

Integrins mediate cell-matrix interactions, anchoring cells to the ECM and enabling migration. Cadherins maintain cell-cell adhesions, contributing to tissue integrity and coordinated movement.

How are integrins and cadherins altered in tumor cells?

<p>Tumor cells often exhibit altered integrin profiles, enhancing motility and survival. Loss of E-cadherin, a type of cadherin, promotes epithelial-to-mesenchymal transition (EMT) and invasion.</p> Signup and view all the answers

What is the role of the extracellular matrix (ECM) in normal cell migration?

<p>The ECM provides a substrate for cell movement and acts as a signaling platform, influencing cell behavior.</p> Signup and view all the answers

How is the ECM altered in tumor cells?

<p>Tumor cells can degrade the ECM using enzymes like matrix metalloproteinases (MMPs), creating invasive pathways and releasing growth factors bound to ECM components.</p> Signup and view all the answers

How does the actin cytoskeleton contribute to normal cell migration?

<p>The actin cytoskeleton drives protrusion and contractility, enabling cells to move forward and retract their rear ends.</p> Signup and view all the answers

What are the key features of lamellipodia, filopodia, and stress fibers in cell migration?

<p>Lamellipodia are sheet-like protrusions that probe the environment and push the cell forward. Filopodia are finger-like projections that sense directional cues. Stress fibers generate contractile force and support cell rear retraction.</p> Signup and view all the answers

How are Rho GTPases involved in normal cell migration?

<p>Rho GTPases act as molecular switches regulating actin cytoskeleton dynamics, influencing cell shape, adhesion, and motility.</p> Signup and view all the answers

Describe the roles of Rac1, RhoA, and Cdc42 in cell migration.

<p>Rac1 promotes lamellipodia formation, facilitating actin polymerization at the leading edge. RhoA regulates stress fiber formation and focal adhesion maturation, contributing to rear retraction. Cdc42 promotes filopodia formation, coordinating polarity during migration.</p> Signup and view all the answers

What are the two main cell types found in tumor tissues?

<p>The two main cell types are the parenchyma, which constitutes the tumor cells themselves, and the stroma, which includes surrounding connective tissue support cells, immune cells, and vasculature.</p> Signup and view all the answers

What is the significance of integrin signaling in cancer?

<p>Integrin binding to the ECM activates downstream signaling pathways, including the focal adhesion kinase (FAK) and the Src kinase, leading to increased cell survival, proliferation, and migration.</p> Signup and view all the answers

What are MMPs and TIMPs, and how are they related to metastasis?

<p>MMPs are proteases that degrade the ECM, facilitating invasion and metastasis. TIMPs are inhibitors of MMPs, which can limit tumor cell invasion.</p> Signup and view all the answers

Explain the "seed & soil" theory of metastasis.

<p>This theory suggests that successful metastasis depends on a productive interaction between cancer cells (the seed) and the surrounding tissues (the soil) which provide appropriate growth factors and ECM components.</p> Signup and view all the answers

What is EMT, and how is it related to metastasis?

<p>EMT is a process where epithelial cells lose their epithelial characteristics and acquire mesenchymal features, such as motility and invasiveness. This transition is often associated with increased metastatic potential.</p> Signup and view all the answers

What factors influence the spread of cancer to specific sites?

<p>Cancer cells often spread to specific sites based on factors such as venous and lymphatic drainage patterns, as well as the presence of body cavities that allow tumor cells to shed and metastasize.</p> Signup and view all the answers

What are some challenges in studying metastasis, and how are they addressed?

<p>Challenges include difficulty in replicating human metastasis in animal models. To address this, experimental systems have been developed, such as using fragments of human bone implanted into immunocompromised mice for studying bone metastasis.</p> Signup and view all the answers

Which of the following is NOT a characteristic of epithelial cells?

<p>Motility</p> Signup and view all the answers

Which of the following statements about MMPs is CORRECT?

<p>MMPs require zinc for activity</p> Signup and view all the answers

What is the role of B-catenin in EMT?

<p>B-catenin is a transcription factor involved in regulating gene expression. During EMT, loss of E-cadherin frees B-catenin, leading to increased levels of B-catenin and altered transcription of genes crucial for cell proliferation, differentiation, and other processes.</p> Signup and view all the answers

Dysregulation of Rho GTPases in cancer can promote increased invasive and metastatic capabilities.

<p>True</p> Signup and view all the answers

Which of the following is NOT a characteristic of mesenchymal cells?

<p>Expression of cadherins</p> Signup and view all the answers

Which of the following is an example of an experimental system used to study bone metastasis?

<p>Implanting fragments of human bone into immunocompromised mice and injecting human prostate cancer cells</p> Signup and view all the answers

Match the following proteins with their respective functions:

<p>Integrins = Mediate cell-matrix interactions Cadherins = Maintain cell-cell adhesions MMPs = Degrade the ECM TIMPs = Inhibit MMP activity</p> Signup and view all the answers

Study Notes

Invasiveness vs. Metastasis

  • Invasiveness is the ability of cancer cells to penetrate surrounding tissues
  • Metastasis is the spread of cancer cells from a primary tumor to distant organs, forming secondary tumors.
  • Cancer cells must acquire the ability to move and navigate physical barriers (extracellular matrix, or ECM).

Cellular Systems in Normal & Tumor Cell Movement

  • Adhesion Molecules:
    • Integrins: Dimers that mediate cell-matrix interactions. In normal cells, they anchor to the ECM. In cancer, altered integrin profiles enhance motility and survival.
    • Cadherins: Maintain cell-cell adhesions. In normal cells, they help with migration. In cancer, loss of E-cadherin promotes epithelial-mesenchymal transition (EMT) and invasion.
  • Extracellular Matrix (ECM): Substrate for movement. In normal cells, it supports migration. In cancer, it's degraded by MMPs to create invasion pathways
  • Actin Cytoskeleton: Drives protrusion and contractility in normal cells. Dysregulation enhances invasive behavior.
  • Lamellipodia & Filopodia:
    • Lamellopodia: Probes the environment, pushing the cell forward. Activated by Rac.
    • Filopodia: Senses directional cues for migration. Activated by Cdc42.
  • Stress Fibers & Focal Contacts:
    • Stress fibers: Generate contractile force, support rear retraction. Activated by RhoA.
    • Focal contacts/adhesion: Specialized sites where integrins connect to the ECM and actin cytoskeleton.
  • Rho Family GTPases: Molecular switches regulating cytoskeletal dynamics, crucial for normal cell movement.
    • Rac1: Promotes lamellipodia formation, actin polymerization. Altered activity promotes invasion.
    • RhoA: Regulates stress fiber formation, focal adhesion maturation, important for rear contraction. Abnormal activity promotes migration.
    • Cdc42: Promotes filopodia formation, coordinates polarity during migration by directing actin dynamics and microtubule organization.

Tumor Cell Types

  • Parenchyma: The tumor cells themselves.
  • Stroma: Surrounding connective tissue (fibroblasts), immune cells, and vasculature.

Integrin Signaling

  • Integrin binding to the ECM activates FAK (focal adhesion kinase).
  • FAK then autophosphorylates, activates other signaling proteins.
  • Src is needed for integrin-mediated motility (via CAS/CRK/DOCK180 activation).
  • Grb2 activates the Ras/Raf/MEK/ERK (MAPK) pathway, affecting transcription.
  • Ras can also activate PI3K, promoting cell survival.
  • Rac, Rho, Cdc42 (small GTPases) are related to Ras but affect cytoskeleton function, movement, and Raf activation.

MMPs & TIMPs

  • Matrix Metalloproteinases (MMPs): Proteases that break down the ECM (require zinc).
  • TIMPs (Tissue Inhibitors of Metalloproteinases): Inhibit MMP activity.
  • MMP activity promotes invasion/metastasis. TIMPs inhibit.
  • MMPs can release growth factors (e.g., VEGF) bound to ECM proteins, promoting localized signaling.

"Seed & Soil" Theory of Metastasis

  • Proposes that successful metastasis depends on the interaction between cancer cells ("seed") and the receptive tissues ("soil"), that provide appropriate growth factors and ECM.
  • Some tumor cells may preferentially adhere and grow in certain organs.

Epithelial-Mesenchymal Transition (EMT)

  • EMT is a cellular process where epithelial cells gain mesenchymal characteristics.
  • Loss of E-cadherin, cell polarity, and intermediate filament expression.
  • Acquisition of fibroblast shape, motility, invasiveness, mesenchymal gene expression, N-cadherin, MMP-2/MMP-9, fibronectin secretion, and PDGF/αvβ6 integrin expression.
  • Loss of E-cadherin releases β-catenin (transcription factor); increased β-catenin levels influence gene expression linked to proliferation, differentiation, etc.
  • EMT is associated with increased invasiveness and metastatic potential.

Factors Influencing Metastasis to Specific Sites

  • Cancer spread is often linked to specific venous drainage sites and body cavities.

Challenges in Studying Metastasis

  • Difficulty replicating metastasis in animal models (e.g., xenografts) due to differences in human and mouse biology.
  • Bone metastasis difficulty; fragments of human bone with human prostate cancer cells were injected into immunocompromised mice.

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Description

This quiz explores the concepts of invasiveness and metastasis in cancer, highlighting the differences between these two processes. Learn how cancer cells manipulate cellular systems, including adhesion molecules and the extracellular matrix, to promote tumor spread and invasion.

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