Cancer Biology: Stem Cell Hypothesis

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Questions and Answers

What characteristic distinguishes cancer stem cells from regular tumor cells?

Higher rate of apoptosis

Properties of self-renewal and multi-potency (correct)

Inability to form new tumors

Ability to solely proliferate

How does the cancer stem cell hypothesis redefine the understanding of cancer?

It posits that cancer is fundamentally a stem cell disorder. (correct)

It identifies apoptosis as the primary cause of tumor evolution.

It suggests that cancer is strictly a genetic disorder.

It emphasizes that tumor growth is solely due to external factors.

What role does the tumor microenvironment play in the behavior of cancer stem cells?

It restricts the plasticity of cancer stem cells.

It facilitates interactions that can enhance cancer stem cell survival and proliferation. (correct)

It has no impact on cancer stem cell functions.

It primarily promotes apoptosis in tumor cells.

What is a common mechanism of drug resistance observed in cancer stem cells?

Upregulation of drug efflux transporters Signup and view all the answers

What factor contributes to the plasticity of cancer stem cells?

The ability to respond to microenvironmental signals Signup and view all the answers

Which of the following markers is associated with cancer stem cells in acute myelogenous leukemia (AML)?

CD34+, CD38- Signup and view all the answers

What characteristic of cancer stem cells (CSCs) allows them to form a heterogenous tumor repeatedly?

Self-renewal Signup and view all the answers

Which property of cancer stem cells contributes to their resistance to therapies?

Long-lived cells Signup and view all the answers

Which method is typically used to assess the frequency of cancer stem cell populations?

Limiting dilution assay Signup and view all the answers

How are cancer stem cells primarily influenced in their behavior and characteristics?

Extracellular signals Signup and view all the answers

Which surface marker combination is identified in breast cancer stem cells?

CD44+ and CD24- Signup and view all the answers

What is a significant challenge in targeting cancer stem cells therapeutically?

Unique genetic profiles Signup and view all the answers

In which state do cancer stem cells predominantly exist within the cell cycle?

Quiescent state Signup and view all the answers

Which of the following characteristics is associated with higher lineage cancer stem cells (CSCs)?

Increased aggressiveness Signup and view all the answers

In the context of cancer stem cells, what role does the niche play following cell division?

It dictates the fate of CSCs. Signup and view all the answers

What can promote the expansion of cancer stem cells?

Loss of niche dependency Signup and view all the answers

How do cancer stem cells contribute to metastasis?

By mediating plasticity and migration Signup and view all the answers

What is a therapeutic implication of targeting cancer stem cells?

Targeting resistant cell populations Signup and view all the answers

How do cancer stem cells evade therapy?

By enhancing self-renewal and resistance properties Signup and view all the answers

What is a significant trait of cancer stem cells in relation to their plasticity?

They can adapt to different environments. Signup and view all the answers

What indicators suggest a poor prognosis in cancer stem cells?

High enrichment of CSC phenotypes following therapy Signup and view all the answers

Study Notes

Historical Views On Cancer

Cancer is a proliferative disease that involves a disruption of normal tissue
Cancer cells exhibit increased expression of genes promoting proliferation while suppressing growth inhibitory genes.
Cancer cells display an inability to undergo programmed cell death (apoptosis).

Cancer Stem Cell Hypothesis

Tumours originate from cancer stem cells (CSCs)
CSCs possess properties of normal stem cells, including self-renewal and multipotency.
The unregulated growth of cancer is attributed to disruptions in stem cell renewal.
Cancer is viewed as a stem cell disorder, not solely a disruption in cell proliferation or death.

Discovery of CSCs

The concept of CSCs emerged in 1994.
Dr. John Dick, from the University of Toronto, identified a small subpopulation of cells within a leukemic sample that possessed the ability to reconstitute the entire tumor.
This discovery suggested that these 'immature' cells, distinct from the bulk tumor mass, held unique properties.

Higher Lineage CSCs and Prognosis

The presence of higher lineage CSCs is linked to a poor prognosis and increased tumor aggressiveness.
CSCs are often characterized by specific cell surface markers, serving as potential targets for therapy.

Plasticity of CSCs

CSCs exhibit plasticity, meaning they can transition between different states.
This plasticity involves changes in their differentiation, self-renewal, and response to therapy.
This plasticity is crucial for understanding their role in tumor development and metastasis.

CSC Niche and Fate

The microenvironment surrounding CSCs, known as the niche, plays a crucial role in regulating their fate.
CSCs receive signals from the niche, influencing their self-renewal, differentiation, and survival.
CSCs also engage in communication with the niche by releasing signals that influence the microenvironment.

Niche Dependency and CSC Expansion

Loss of niche dependency can promote CSC expansion and tumor growth.
Factors in the niche can create a supportive environment for CSCs, promoting their survival, proliferation, and resistance to therapy.

CSCs and Metastasis/Relapse

CSCs are implicated in driving metastasis and relapse of cancer.
Presence of CSC markers in bodily fluids and metastatic sites suggests their involvement in metastasis.
Studies have shown increased enrichment of CSC phenotypes following treatment, suggesting their role in treatment resistance.

Therapeutic Implications of CSCs

CSCs pose a challenge to conventional therapy due to their resistance to treatment modalities.
CSCs are the driving force behind metastasis and relapse.
Specific therapies targeting CSCs offer promise for achieving complete remission and preventing tumor recurrence.

How CSCs Evade Therapy

CSCs employ various mechanisms to evade therapy, contributing to their resistance.
These mechanisms often involve their quiescent state (non-dividing) and unique expression of drug resistance proteins.

Stem Cell Characteristics of CSCs

CSCs share several key characteristics with normal stem cells, including:
- Self-renewal: The ability to divide and create copies of themselves.
- Multipotency: The capacity to differentiate into different cell types.
- Long lifespan: Their ability to survive for extended periods.

Identifying Properties of CSCs

CSCs exhibit specific properties that distinguish them from other cancer cells.
These include:
- The ability to form a heterogeneous tumor containing various cell types.
- High proliferation potential.
- Resistance to therapy.
- Sensitivity to signals from their microenvironment (niche).
- Quiescence, or a non-dividing state.
- Specific cell surface markers.

Methods for Identifying CSCs

Various methods are employed to identify and study CSCs in research:
- Sphere-forming assays: This method assesses the ability of cells to form spheres in a specific culture environment, providing an indication of the number of CSCs present.
- Flow cytometry: A technique used to sort cells based on specific markers.
- Xenotransplantation: This method involves transplanting cells into immune-deficient animals, providing a model to study tumor growth and metastasis.

CSC Markers

Identification of cell surface markers has significantly advanced CSC research.
These markers have been utilized for isolating and studying CSC populations in different cancer types.
Some examples include:
- Acute myeloid leukemia: CD34+, CD38-
- Breast cancer CD44+, CD24-/low, Lin-, ALDH+
- Brain cancer: CD133+, CD44+, CD15+
- Prostate cancer: CD44+
- Colon cancer: CD133+

Initial Evidence of CSCs in Solid Tumors

The groundbreaking research involving breast cancer provided the first evidence of CSCs in solid tumors.
Cells sorted from breast cancer patient samples were found to have distinctive properties with respect to their ability to form tumors.

CD44+ CD24- Cells and Tumourigenic Properties

Within breast cancer samples, cells expressing CD44+ and CD24- markers exhibited strong tumourigenic properties.
Even small numbers of these cells (as few as 100) were capable of forming tumors.
This observation highlighted the importance of CSCs in breast cancer development.

Breast CSCs Recapitulate Heterogenous Tumors

CSCs derived from breast cancer patient samples, when serially passaged in mice, were able to recapitulate the heterogenous nature of the original tumors.
This observation further supported the concept that CSCs drive tumor heterogeneity.
Further research is needed to explore the role of other markers and the diverse nature of CSCs.

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Description

Explore the pivotal concepts in cancer biology, focusing on the cancer stem cell (CSC) hypothesis. This quiz delves into the characteristics of cancer cells, the discovery of CSCs, and their implications in tumor formation and treatment. Understand how disruptions in normal stem cell functions contribute to cancer pathology.