Cancer-Associated Fibroblasts Research Quiz
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Questions and Answers

What is the primary focus of the research presented in Nature Communications?

  • Development of new cancer therapies
  • Genetic modifications in cancer cells
  • Coordination of cancer-associated fibroblasts (CAFs) (correct)
  • Effects of cancer treatments on fibroblasts

Fibronectin is shown to play a role in the mechanical properties of CAFs.

True (A)

What method was used to quantify mean normal tractions per pillar?

Kruskal-Wallis ANOVA test and Dunn's multiple comparisons test

CAFs are known for their role in ________ coordination in the tumor microenvironment.

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

Match the following variables to their respective measurements:

<p>Normal tractions = Measured in Pa Cluster area = Normalized to initial size Cell density = Counted per image Time = Measured in hours</p> Signup and view all the answers

The mean ________ per pillar was averaged across pillar height.

<p>normal tractions</p> Signup and view all the answers

What was used to stain DNA in the representative images?

<p>DAPI (B)</p> Signup and view all the answers

What is the primary function of cancer-associated fibroblasts (CAFs) in tumors?

<p>Enhancing cancer cell invasion (C)</p> Signup and view all the answers

Fibroblasts only have a supportive role in the tumor microenvironment.

<p>False (B)</p> Signup and view all the answers

What method was used to assess CAF pillar compression in this research?

<p>A drop containing pre-stained CAFs was added on top of pillar-containing PAA gel.</p> Signup and view all the answers

CAFs can increase resistance to __________ agents.

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

Match the following researchers with their focus area regarding CAFs:

<p>Sahai, E. = Framework for understanding CAFs in cancer Kalluri, R. = Biology and function of fibroblasts in cancer Attieh, Y. = Hallmarks of CAFs in cancer invasion Barbazan, J. = Role of CAFs in cancer invasion mechanics</p> Signup and view all the answers

Which temperature and CO2 concentration were used to incubate the CAFs for attachment?

<p>37 °C, 5% CO2 (D)</p> Signup and view all the answers

CAFs contribute to spatially coordinated migration patterns within a tumor.

<p>True (A)</p> Signup and view all the answers

Name one of the main methods discussed to evaluate the behavior of CAFs in cancer.

<p>Incubating pre-stained CAFs on PAA gels.</p> Signup and view all the answers

What role do cancer-associated fibroblasts play in tumor biology?

<p>They promote tumor invasion (D)</p> Signup and view all the answers

N-cadherin is considered a key regulator of collective cell migration in a 3D environment.

<p>True (A)</p> Signup and view all the answers

What is a significant consequence of concomitant Notch activation and p53 deletion in mouse gut?

<p>Epithelial-to-mesenchymal transition and metastasis</p> Signup and view all the answers

Fibroblasts guide carcinoma collective migration through __________-guided mechanisms.

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

Match the following entities with their roles:

<p>Cancer-associated fibroblasts = Promote tumor invasion N-cadherin = Regulates collective cell migration Notch pathway = Triggers epithelial-to-mesenchymal transition Fibronectin = Guides cell migration</p> Signup and view all the answers

Which of the following methods were employed to study cell migration in tissues?

<p>Live imaging and explant culture (B)</p> Signup and view all the answers

Directional cancer cell migration is enhanced by misalignment of fibronectin in the tumor microenvironment.

<p>False (B)</p> Signup and view all the answers

What cellular structure forms contacts involving fibronectin among fibroblasts?

<p>Stitch adhesions</p> Signup and view all the answers

Flashcards

Tumour Budding

Small clusters of cancer cells that detach from the main tumor mass and invade surrounding tissue. It's a sign of aggressive tumor behavior and potential metastasis.

Tumour Microenvironment

The complex network of cells, proteins, and factors surrounding a tumor. It includes other cancer cells, immune cells, blood vessels, and the extracellular matrix.

Epithelial-to-Mesenchymal Transition (EMT)

A process where epithelial cells, which normally form tight junctions, transform into mesenchymal cells, which are more migratory and invasive.

Fibronectin

A protein found in the extracellular matrix that helps guide cell migration.

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Integrin

A protein on the cell surface that binds to fibronectin and other extracellular matrix proteins, allowing cells to attach and migrate.

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Cancer-Associated Fibroblasts (CAFs)

Fibroblasts that have been altered by the tumor microenvironment and contribute to tumor growth and metastasis.

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Stitch Adhesions

Specialized cell-cell contacts formed by fibroblasts that involve fibronectin and promote cell migration.

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Explant Culture

A technique for studying cell migration in a 3D environment by using a small piece of tissue (explant) that contains cells and their surrounding matrix.

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CAF Traction Forces

The mechanical forces exerted by cancer-associated fibroblasts (CAFs) on their surroundings, influencing cellular behavior and tumor microenvironment.

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Fibronectin Scaffolds

Extracellular matrix proteins that provide structural support and influence cell adhesion, migration, and communication in the tumor microenvironment.

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N-cadherin Depletion

The reduction or absence of N-cadherin, a cell adhesion molecule, in CAFs, leading to altered cell-cell interactions and potentially affecting their collective behavior.

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CAF Supracellular Coordination

The organized and coordinated behavior of multiple CAFs working together to influence tumor growth and progression.

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Traction Maps

Visual representations of the forces exerted by cells on their substrate, providing insights into cell behavior and interactions.

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Cancer Cell and CAF Co-cultures

In vitro experimental systems where cancer cells and CAFs are grown together to mimic the interactions observed in tumors.

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CAF Ring Area

The area occupied by a ring-shaped cluster of CAFs, potentially indicating their collective involvement in tumor growth and invasion.

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Radial Traction Peak Magnitude

The maximum force exerted by CAFs at the boundary of a cluster, reflecting their influence on surrounding cells and the tumor microenvironment.

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CAF Compression

A method to quantify the density of Cancer-Associated Fibroblasts (CAFs) within a 3D microenvironment by measuring their ability to compress a soft gel.

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CellTracker Green

A fluorescent dye used in cell biology to label cells, making them visible under a microscope. In this context, it stains CAFs green for analysis.

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PAA Gel

A type of synthetic gel used to create a 3D environment for cells. It allows cells to grow and interact in a more natural context than a flat surface.

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CAF Attachment

The process by which CAFs adhere to the PAA gel, forming a stable connection. This is essential for studying their behavior in the 3D context.

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Incubation

The controlled process of keeping cells at a specific temperature (37°C) and atmosphere (5% CO2) to mimic the conditions found within the human body.

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Proliferation

Cell multiplication or growth. In the context of this research, scientists can study how the mechanical environment affects the rate at which cells divide.

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Chemotherapeutic Agents

Drugs used to treat cancer by killing cancer cells. This research investigates how the mechanical environment can affect the effectiveness of these drugs.

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Nuclear Envelope Integrity

The structural integrity of the membrane surrounding the nucleus of a cell. This is important for maintaining the cell's genetic material and function.

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Study Notes

Cancer-Associated Fibroblasts (CAFs)

  • CAFs accumulate in tumors, producing excess extracellular matrix (ECM) forming a capsule around cancer cells.
  • This capsule restricts tumor growth by increasing intratumoral pressure.
  • CAFs are not passive; they actively compress cancer cells via actomyosin contractility.
  • Loss of CAF contractility impairs capsule formation and dissipates compressive forces.
  • CAF force patterns are independent of cancer cell growth.
  • Fibronectin cables facilitate force transmission between CAFs.

Mechanotransduction

  • Cancer cells sense CAF compression, affecting transcriptional regulator YAP localization and proliferation.
  • Cancer progression involves complex interactions between cancer cells and their microenvironment.
  • This includes biochemical signals from stromal cells and physical cues (ECM stiffness, pressure, stress).
  • CAF activity plays a significant role in modulating cancer cell survival, proliferation, invasion and immune response.

In Vivo and In Vitro Studies

  • Transgenic mice (N/p53/mTmG) were used to analyze CAF organization and tumor compartmentalization.
  • CAFs are essential for forming intratumoral capsules which compartmentalize and confine cancer cells.
  • In vitro co-culture systems mimicking tumor organization were developed using PDX-derived cancer cells and CAFs.
  • CAFs form a ring around cancer cell clusters, causing cell deformation and multilayering.
  • Traction force microscopy (TFM) revealed radial compressions by CAFs at the tumor-stroma interface.
  • Negative radial forces progressively increase as a CAF ring forms around the cancer cell cluster.
  • The process of CAF ring closure is related to increased stress, tissue shear and eventually a yield stress-like deformation of the cancer cell cluster.
  • CAFs' contractility is essential for capsule formation; myosin IIA knockout CAFs exhibited reduced force.

CAF-Cancer Cell Interactions

  • CAF compression is dependent on active actomyosin contractility.
  • The loss of CAF contractility impacts YAP localization, reducing nuclear accumulation and increasing cytoplasmic retention.
  • Loss of CAF-mediated compression resulted in enhanced YAP nuclear accumulation and cancer cell proliferation.
  • Fibronectin plays a crucial role in CAF supracellular coordination through cable formation, enabling force transmission.

Mechanical Interactions

  • Laser ablations were performed to assess local tissue displacements, with compression influencing cancer cell displacement and CAF recoil.
  • CAF compression affects cancer cell proliferation rather than apoptosis.

Additional Findings

  • Fibroblasts (including intestinal fibroblasts) also exhibit compression on cancer cells, suggesting a broad mechanical influence.
  • CAF compression reorganizes the tumor's morphology and affects the distribution of the mechanosensor YAP in cancer cells.
  • CAF compression affects cancer cell growth via reduced proliferation and potentially increased apoptosis.

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Related Documents

Cancer-Associated Fibroblasts Actively Compress Cancer Cells (2023) - PDF

Description

Test your knowledge on the role of cancer-associated fibroblasts (CAFs) in the tumor microenvironment. This quiz covers topics such as mechanical properties, methods used in research, and the functions of CAFs. Dive into the details of how CAFs contribute to tumor dynamics and resistance to therapies.

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