Cancer Biology: Cell Dissemination & ECM

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Questions and Answers

What role does the extra-cellular matrix (ECM) play in cellular signaling?

It is only responsible for buffering action within organs.

It acts exclusively as a barrier without any structural support.

It provides tracks for cell movement and binds growth factors to their receptors. (correct)

It prevents any movement of cells within tissues.

Which statement correctly describes the characteristics of basement membranes?

They primarily consist of type I collagen and do not provide cell anchorage.

They separate endothelia and epithelia from connective tissue and can be modified for specialized functions. (correct)

They are static structures and do not undergo modifications.

They lack any influence on cell polarization and tissue morphology.

What best describes the role of the ECM in relation to organ structure?

It solely provides hydration without any structural function.

It serves as an active regulator of cell behavior and maintains water retention. (correct)

It only provides structural support without influencing cell signaling.

It is irrelevant as organs can function independently of the ECM.

What is a consequence of cancer cell dissemination?

Cancer cells detach and migrate to other tissues to metastasize. Signup and view all the answers

Which characteristic of the ECM is NOT true?

It has a uniform physical and biochemical composition across different tissues. Signup and view all the answers

What is primarily required for optimal cell motility?

An optimal balance of cell adhesion Signup and view all the answers

In the early stages of focal adhesion assembly, which protein is crucial for its formation?

Rac protein Signup and view all the answers

Which factor does NOT influence the protein composition of focal adhesions?

Integrator presence Signup and view all the answers

What role do focal adhesions play during polarized cell migration?

They stabilize cell adhesion to the ECM. Signup and view all the answers

What happens to focal adhesions after the recruitment of specific proteins to integrins?

They may either disassemble or elongate and grow. Signup and view all the answers

What process allows intracellular signals to enhance integrin's ligand-binding activity?

Inside-out signaling Signup and view all the answers

How do integrins contribute to cell migration?

By regulating actin polymerization and dynamics Signup and view all the answers

What is the significance of localized activation of intracellular signaling by integrins?

It enables polarized cell migration through spatial regulation Signup and view all the answers

What role do adhesions in cell protrusions near the leading edge play in migration?

They regulate actin polymerization and protrusion localization Signup and view all the answers

What functional aspect of integrins is affected by engagement with the matrix?

They impact integrin activation states through bi-directional signaling Signup and view all the answers

What characterizes the RhoA activation switch in relation to cell signaling?

It is a switch from Rac signaling. Signup and view all the answers

What is the leading edge of a migrating cell?

The front edge of the migrating cell. Signup and view all the answers

Which statement best describes focal adhesion (FA) maturation?

Focal adhesion is ready to be disassembled for new FA formation. Signup and view all the answers

What role do lamellipodia play in cell migration?

They adhere to the substrate through focal adhesions. Signup and view all the answers

What are integrins primarily composed of?

Alpha and Beta heterodimers. Signup and view all the answers

How is the specificity of integrin binding determined?

By the extracellular domain. Signup and view all the answers

What signaling mechanism do integrins use to regulate intracellular signaling?

Outside-in signaling. Signup and view all the answers

What happens to integrins when they engage with the extracellular matrix (ECM)?

They are activated. Signup and view all the answers

What is the main function of matricellular proteins in the ECM?

Modulate cell-matrix interactions and cell functions Signup and view all the answers

Which of the following is NOT a member of the matricellular family?

Fibrillin Signup and view all the answers

What is a key role of the ECM during developmental processes?

Facilitating processes like angiogenesis Signup and view all the answers

How do cells respond to changes in the biomechanical properties of the ECM?

They modify their interactions with the ECM. Signup and view all the answers

What happens to focal adhesions (FAs) during cell migration?

They persist as anchors until the cell moves over them. Signup and view all the answers

What characterizes the dynamic structures of focal adhesions?

They are located in lamellipodia regions and have rapid turnover. Signup and view all the answers

Defects in ECM dynamics are associated with what potential health issue?

Cancer development Signup and view all the answers

What is the role of integrins in cell-matrix interactions?

They facilitate the formation of focal adhesions. Signup and view all the answers

Study Notes

Cancer Cell Dissemination

Cancer cell dissemination is a process where cancer cells detach and migrate from the primary tumor to metastasize.
The primary site contains the tumor mass.
Passive and active intravasation occur in the primary site.
The distant site involves the outgrowth of metastasis, EMT, proteolytic enzymes, dormancy, anoikis, shear stress, and the immune system.
MET and transendothelial migration occur at the distant site.

Composition of the Extracellular Matrix (ECM)

The ECM is present in all tissues and organs.
It provides strength and elasticity to organs, protecting them by maintaining water retention and extracellular homeostasis.
The physical, topological, and biochemical composition of the ECM is tissue-specific.
The ECM provides architectural structure support, functions as a barrier, and is an anchorage site.
It provides tracks for cell movement.
Specialized ECM, basement membranes, separate endothelia and epithelia layers from the underlying connective tissue.
Most basement membranes are composed of type IV collagen, laminin, and other glycoproteins.
The composition and structure of basement membranes can be modified to create specialized or context-specific assemblies.
It's an active regulator of cell polarization and shape tissue morphology.
Changes to basement membranes' deposition, structure, and composition might organize tissue architecture.
Matricellular proteins are another group of ECM molecules.
Examples include thrombospondin 1 and 2, SPARC (osteonectin), and tenascin-C.
Plasminogen activator inhibitor type-1 (PAI-1) and osteopontin modulate cell-matrix interactions and cell functions, but do not function as structural elements.
The ECM is constantly remodeled to meet tissue needs and matrix remodeling.
Its importance is especially seen in developmental processes like branching morphogenesis and angiogenesis.
Cells respond to differences in biomechanical properties of the matrix.
The interaction between cells and the ECM is highly dynamic.
Defects in regulating ECM dynamics can affect tissue homeostasis and contribute to cancer.

Cell-Matrix Interactions

Cell adhesion to the substrate surface elicits integrin-mediated Focal Adhesion (FA) formation to connect the ECM with intracellular signaling and cytoskeletal complexes.
Cell-substrate adhesions occur at both forward and rearward ends of the cell, facilitating forward migration.
FAs formed at the cell front persist as cell-ECM anchors until the cell body migrates over the FAs, reaching the cell rear.
The sequence of events involves symmetry breaking, protrusion and new adhesion at the front, and retraction of the rear.

Focal Adhesions

FAs are dynamic structures located in lamellipodia regions, with a capacity for rapid turnover.
They generate traction forces and organize signals from the ECM to the cell, triggering cell survival, proliferation, and migration pathways.
FAs are formed through the recruitment of signaling and structural proteins to activated integrin tails at the plasma membrane-ECM interface.
The protein composition of adhesions fluctuates even within a single adhesion and depends on adhesion age, ECM composition, and substrate tension.
Cell motility requires an optimal balance of cell adhesions: too little, cells can't generate enough traction to move; too much, cells cannot translocate.
During polarized cell migration, FAs stabilize cell adhesion to the ECM, allowing for actomyosin contraction and cell body translocation.
Early stages of FA assembly are Rac protein-dependent.
This process involves sequential recruitment of proteins like talin, paxillin, vinculin, α-actinin, FAK, and VASP to integrins.
At a certain point, the FA may disassemble or elongate and grow, characterized by RhoA activation from Rac signaling and local mechanical force generated by actomyosin contractility (actin filament contraction).
Leading and trailing edges define the front and rear of migrating cells, respectively.
FA maturation involves the formation and subsequent disassembly of the adhesion complex, allowing new formation in the leading edge.
Lamellipodia adhere to the substrate through FA formation combined with actomyosin contraction, generating forces from retrograde actin flow.
The process allows forward propulsion and translocation of the cell body.

Integrins

Integrins are alpha and beta heterodimers formed by selective pairing between alpha and beta subunits (18).
They join the cytoskeleton inside the cell to the extracellular matrix outside the cell.
Integrins contain a large extracellular domain that binds to the ECM and links the actin cytoskeleton through a short cytoplasmic tail.
There are 24 distinct integrin receptors.
Binding specificity is determined by the extracellular domain recognizing various matrix ligands.
Integrins bind to specific motifs within matrix proteins.
Changes in integrin repertoire correlate with changes in migration mode and invasive phenotypes.
Integrins lack intrinsic catalytic activity; they are activated upon engagement with the ECM.
Integrins provide a bi-directional conduit for mechanochemical information across the cell membrane, linking the ECM with the cell interior.
Integrin-mediated cell adhesion transmits information to intracellular signaling pathways, crucial for cell spreading and migration.
Intracellular signals can induce integrin conformational changes, prolonging ligand-binding activity (inside-out signaling).
Integrin engagement with the matrix affects integrin activation and allows for bidirectional crosstalk between inside-out and outside-in signaling.
Integrin-containing adhesion centers orchestrate signalling pathways for cell migration.
Rho GTPases regulate actin polymerization, dynamics, and adhesion.
Signaling by adhesions is highly localized and drives polarized migration.
Adhesions in protrusions, especially near the leading edge, regulate actin polymerization and localize protrusions.
Transient localized activation of intracellular signaling by integrins contributes to spatial and temporal polarized cell migration.

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Description

Explore the processes of cancer cell dissemination and the role of the extracellular matrix (ECM) in tissue architecture. This quiz covers vital concepts related to how cancer cells metastasize and the composition and functions of the ECM. Test your understanding of these critical aspects of cancer biology.