Cancer Invasiveness and Metastasis Overview

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Questions and Answers

What distinguishes invasiveness from metastasis in cancer progression?

Invasiveness refers to the spread of cancer cells to distant organs.

Invasiveness involves the formation of primary tumors.

Invasiveness is only related to secondary tumors.

Invasiveness involves penetrating surrounding tissues, while metastasis spreads to distant sites. (correct)

Which proteins are predominantly altered in cancer that impact cell adhesion?

Integrins and cadherins (correct)

Histones and transcription factors

Collagen and elastin

Neurotransmitters and hormones

What role do matrix metalloproteinases (MMPs) play in cancer cell behavior?

MMPs are solely responsible for initiating tumor formation.

MMPs facilitate the degradation of extracellular matrix components. (correct)

MMPs enhance the structural integrity of cellular barriers.

MMPs inhibit cancer cell proliferation.

Which of the following cellular structures is primarily involved in the movement of cancer cells?

The actin cytoskeleton Signup and view all the answers

Which of the following terms describes the process of cancer cells entering blood vessels?

Intravasation Signup and view all the answers

What is the primary role of integrins in relation to cancer cell dynamics?

Mediating interactions between cells and the extracellular matrix (ECM) Signup and view all the answers

The process of epithelial-mesenchymal transition (EMT) leads to all of the following EXCEPT:

Increased E-cadherin expression Signup and view all the answers

How do Matrix Metalloproteinases (MMPs) influence cancer metastasis?

They break down the ECM, facilitating tumor invasion. Signup and view all the answers

Which family of proteins is primarily involved in regulating actin cytoskeleton dynamics?

Rho family GTPases Signup and view all the answers

What theory explains why certain tumor cells metastasize better to specific organs?

Seed and Soil theory Signup and view all the answers

Which actin structure is primarily involved in sensing directional cues during cell migration?

Filopodia Signup and view all the answers

What is the significance of Focal Adhesions in cancer cell migration?

They serve as connections between integrins and the actin cytoskeleton. Signup and view all the answers

Which protein is primarily responsible for promoting lamellipodia formation during cell migration?

Rac1 Signup and view all the answers

What effect does the deletion of E-cadherin have on cancer cells?

It increases cell motility and invasiveness. Signup and view all the answers

Which of the following is NOT typically associated with tumor stroma?

Tumor-specific markers Signup and view all the answers

How does Src contribute to integrin-mediated motility?

Through activation of focal adhesion kinase (FAK). Signup and view all the answers

What key feature of the extracellular matrix (ECM) is directly influenced by MMP activity?

Degradation and remodeling of the ECM Signup and view all the answers

What cellular process is directly promoted by the activation of Ras?

Cell motility and proliferation 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 the primary tumor to distant organs/tissues, forming secondary tumors.

Cellular Mechanisms in Cancer Cell Movement

Adhesion Molecules:
- Integrins: Cell-matrix adhesion, crucial for normal migration; altered in cancer for enhanced motility and survival.
- Cadherins: Maintain cell-cell junctions; loss of E-cadherin promotes epithelial-mesenchymal transition (EMT) and invasion.
Extracellular Matrix (ECM):
- Substrate for cell movement; degraded by Matrix Metalloproteinases (MMPs) to enable invasion.
Actin Cytoskeleton:
- Drives cell protrusion and contraction; dysregulation promotes invasive behavior.
- Lamellipodia: Probe the environment, pushing the cell forward.
- Filopodia: Sense directional cues, guiding migration.
- Stress fibers: Generate contractile force, for cell rear retraction.
- Focal Contacts: Connect ECM to actin cytoskeleton.
Rho Family GTPases:
- Molecular switches regulating actin. Aberrant activity promotes uncontrolled migration.
  - Rac1: Promotes lamellipodia formation.
  - RhoA: Regulates stress fiber formation and focal adhesion maturation.
  - Cdc42: Promotes filopodia formation.

Tumor Cell Types

Parenchyma: The tumor cells themselves.
Stroma: Surrounding connective tissue, immune cells, and vasculature.

Integrin Signaling

Integrin binding to ECM activates FAK (Focal Adhesion Kinase), which can activate downstream signaling pathways (Src, Grb2, Ras, PI3K), impacting transcription, proliferation, and survival.

MMPs and TIMPs

Matrix Metalloproteinases (MMPs): Proteases that degrade the ECM, crucial for invasion and metastasis. Require Zn++ for activity.
Tissue Inhibitors of Metalloproteinases (TIMPs): Inhibit MMP activity.

"Seed and Soil" Theory

Metastasis depends on an interaction between cancer cells ("seed") and the environment ("soil") in a distant location. The "soil" provides specific growth factors/ECM allowing cells to survive and proliferate,

Epithelial-Mesenchymal Transition (EMT)

EMT is a process where epithelial cells lose their characteristics and gain mesenchymal features, such as motility and invasiveness.
Key features include loss of E-cadherin (critical for cell-cell contact), changes in cell shape, and production of invasive enzymes (MMPs).
EMT is correlated with increased invasiveness and metastasis.

Factors Influencing Metastasis to Specific Sites

Cancer cells often spread to specific organs based on blood/lymph drainage patterns and interactions with that organ's environment (growth factors, ECM). For example, tumors near body cavities can spread to those cavities.

Challenges in Studying Metastasis

Difficulty in replicating human metastasis in animal models (such as mice).

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Description

Explore the critical concepts of invasiveness and metastasis in cancer progression. This quiz delves into the cellular mechanisms driving cancer cell movement, focusing on adhesion molecules, extracellular matrix interactions, and the role of the actin cytoskeleton. Test your knowledge on how these factors contribute to tumor aggressiveness.