Name: how cancer stem cells drive relapse
Uploaded: 2021-04-07T12:12:02.000Z
Duration: 2 min 40 s
Channel: JoVE

Most cancers contain a non-uniformly distributed and genetically distinct subpopulation of tumor cells.
Some of these cells, called cancer stem cells, possess the characteristics associated with both cancer cells and stem cells. This means that as well as participating in tumor propagation, such cells can self-renew and differentiate into multiple lineages.
A cancer stem cell, or CSC, can undergo asymmetric cell division - where one set of daughter cells retain the stem-cell potential and can divide indefinitely, while the other can undergo only a few rounds of division before terminally differentiating and eventually dying.
A CSC can also secrete elevated levels of vascular endothelial growth factors within a tumor and generate new blood and lymphatic vessels that maintain a continuous supply of nutrients to the growing tumor.
Additionally, cancer stem cells can attain properties such as increased invasiveness and migration ability, which may aid them in establishment of secondary metastatic sites in the body.
Even though cancer stem cells carry the potential to seed new tumors and drive their growth, it is the rapidly dividing non-stem cells that form major components of the tumo

cancer stem cells and tumor maintenance

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in a quiescent state until the receipt of a stimulatory signal, which triggers proliferation or differentiation. Genetic alterations in these normal stem cells can reprogram their cellular pathways, turning them into cancer stem cells. Such cells divide abnormally and contribute to tumor progression while maintaining their stem cell properties.
Cancer stem cells can give rise to more stem cells or highly differentiated cancer cells with equal probability. While the daughter cancer stem cells can seed new tumors or metastasize to new sites, the non-stem cancer cells terminally differentiate and are eventually discarded and replaced after a few rounds of division. However, in most tumors, the differentiated cells form a significant mass of the cancer-cell population.
Cancer stem cells often demonstrate endurance to conventional cancer therapies. Cancer stem cells&#39; ability to increase drug efflux rate, alter drug metabolism, resist DNA damage, and enhance DNA repair to their advantage, is often attributed to their chemo-resistance. Epigenetic modifications and supplementary survival signals from tumor microenvironments also contribute to the drug resistance exhibited by these cancer stem cells.
Hence, the presence of cancer stem cells is understood to be one of the primary reasons for tumor maintenance, cancer-treatment failure, relapse, and even metastasis.

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often ...

Education

JoVE Core

Molecular Biology

Unit 2

Cancer

KEY TERMS AND CONCEPTS

how cancer stem cells drive relapse

Cancer stem cells help tumors survive treatment and return after therapy. These residual cells can remain after early diagnosis and treatment, and they often lead to tumor recurrence. They are important because they can self-renew and also produce more than one cell type, which makes them hard to eliminate.

Cancer stem cells are thought to come from normal stem cells or progenitor cells in a tissue. Normal stem cells usually stay quiet, or quiescent, until a signal tells them to divide or differentiate. If genetic changes alter these cells, their normal pathways can be reprogrammed and they can become cancer stem cells. These altered cells then divide in an abnormal way while still keeping stem cell-like traits.

A cancer stem cell can make either another stem cell or a more differentiated cancer cell with equal probability. The new stem cells can seed a new tumor or spread to another site by metastasis. The non-stem cancer cells keep differentiating, then are eventually removed and replaced after a few rounds of division. Even so, differentiated cells make up a large part of many tumors.

Cancer stem cells are often hard to kill with standard cancer treatments. They may pump drugs out of the cell faster, change how drugs are broken down, resist DNA damage, and repair their DNA more effectively. Epigenetic changes and extra survival signals from the tumor microenvironment can also help them survive. Because of these traits, cancer stem cells are linked to tumor maintenance, treatment failure, relapse, and metastasis.

How Cancer Stem Cells Drive Relapse

what is cancer?

Cancer Cells and How They Spread

Cancer cells and how they spread are explained through the normal behavior of cells and tissues. In a healthy body, cells must coordinate carefully. They rest, grow, divide, differentiate, or die in ways that support the organism. Cancer begins when this control breaks down. Cells divide without stopping and invade nearby tissues or organs. Cancer cells show two heritable traits. They reproduce against normal limits on cell growth and division, and they invade and colonize other cells and...

cancers originate from somatic mutations in a single cell

cancers-originate-from-somatic-mutations-in-a-single-cell

How Mutations Drive Cancer Growth

Cancer develops when mutations change the genes that control the cell cycle and let healthy cells keep dividing. A cancer can begin from a single mutation in one starting cell. As that cell line keeps growing, it can collect more mutations and eventually become malignant. One example is chronic myelogenous leukemia, or CML. It often begins as a non-lethal rise in white blood cells and then grows worse over several years before becoming life-threatening. This shows how cancer can progress step...

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From Polyp to Metastatic Cancer

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Cancer cells survive and spread by gaining genetic changes that help them grow faster than normal cells. These changes build up quickly because defects in DNA repair let mutations appear at an unusually high rate. From an evolutionary point of view, this genetic instability gives cancer cells an advantage as they develop. As mutant cell lines keep changing, they collect helpful mutations that support cancer progression. These cells can divide without fully differentiating, form large cell...

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How Tumors Remodel Their Surroundings

Tumors remodel the local tissue environment to support cancer growth. This surrounding area is called the stroma. It includes several cell types, a basal membrane, and blood vessels. As normal cells mutate and become cancer cells, the nearby environment changes with them. The tumor microenvironment, or TME, is made of the developing tumor and the stromal cells around it. Communication between cancer cells and these surrounding cells is important because it disrupts normal tissue balance and...

metastasis

How Cancer Cells Spread to New Sites

Metastasis is the spread of cancer cells from one part of the body to another. Cancer cells can move through blood vessels, called hematogenous spread, or through lymph vessels. This process helps form tumors in distant tissues. A key step in metastasis is epithelial-to-mesenchymal transition, or EMT. EMT is a normal developmental process seen in wound healing and embryogenesis, but it also appears in cancer metastasis. It is triggered by transforming growth factor-beta (TGF-β) or receptor...

cancer-critical genes i: proto-oncogenes

Oncogenes and Cell Growth Control

Genes usually make proteins that help healthy cells work properly. When mutations change how these genes are expressed, the cell’s traits can change too. If critical genes that control the cell cycle and growth signals are disrupted, cell cycle progress can go off track and cells may divide without control. Over time, these cells can form tumors. Cancer-critical genes are the genes that drive this process. They fall into two main groups: proto-oncogenes and tumor suppressor genes.

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How Retroviruses Trigger Cancer

Retroviruses can trigger cancer by changing how host cells grow and divide. These RNA viruses have been shown to cause cancers in species such as chickens, mice, cats, and monkeys. After infection, the viral RNA genome is reverse-transcribed into DNA. It first becomes single-stranded DNA and then double-stranded DNA. This double-stranded form, called proviral DNA, integrates into the host genome. The host cell then transcribes the proviral DNA along with its own chromosomal DNA. This process...

the ras gene

Ras Proteins: Cellular Switches in Cancer

Ras proteins are small GTPase signaling proteins that help control cell proliferation, differentiation, and cell survival. In humans, the Ras gene family has three main members: HRas, NRas, and KRas. These genes produce four closely related proteins: HRas, NRas, KRas4A, and KRas4B. Ras proteins work like molecular switches. They cycle between an active GTP-bound form and an inactive GDP-bound form. Guanine nucleotide exchange factors, or GEFs, help exchange GDP for GTP and turn Ras on.

loss of tumor suppressor gene functions

Tumor Suppressor Genes and Cancer Risk

Tumor suppressor genes help protect cells from becoming cancerous. They can slow cell division, repair DNA mistakes, or trigger apoptosis, which is programmed cell death, when damage cannot be fixed. These jobs help stop damaged cells from multiplying. When a tumor suppressor gene mutates or is lost, cells may begin to grow out of control. A single working copy is usually enough for the cell to keep normal control of the cell cycle. Cancer develops when both copies are inactivated or lost. <br...

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Cancer stem cells help tumors survive treatment and return after therapy. These residual cells can remain after early diagnosis and treatment, and they often lead to tumor recurrence. They are important because they can self-renew and also produce more than one cell type, which makes them hard to eliminate. Cancer stem cells are thought to come from normal stem cells or progenitor cells in a tissue. Normal stem cells usually stay quiet, or quiescent, until a signal tells them to divide or...

mouse models of cancer study

Mouse Cancer Models in Drug Testing

Mouse cancer models help scientists study how tumors start, grow, and respond to treatment. Mice are widely used because they are similar to humans in many biological and body functions. They are also easy to keep and breed in the laboratory, so many inbred strains are available for research. Cancer research has made major use of genetically modified mice. Transgenic mice carry an added gene, while knockout and knock-in mice have genes deleted or changed with genetic engineering. If a gene...

cancer prevention

Diet and Exercise in Cancer Risk

Diet and exercise can play a major role in cancer risk. Studies show that about 50% of cancer cases may be prevented through a healthy lifestyle, regular exercise, and a modest cancer prevention diet. Populations that eat more fruits and vegetables tend to have lower cancer rates. In contrast, diets high in animal fat, red meat, junk food, or calories are linked with a higher risk of cancer. Plant compounds called phytochemicals may also help protect against cancer. These natural chemicals...

cancer therapies

Combining Cancer Treatments

Cancer treatments often combine surgery, radiation therapy, and chemotherapy. These methods are used to treat cancer patients, but they can also damage normal cells. Cancer cells can also change quickly and become resistant to chemical agents or radiation therapy. Not every cancer responds to the same therapy. Some cancer cells respond to one treatment, while others respond to another because they carry different mutations. The best treatment depends on the type of cancer and how far it has...

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How Targeted Cancer Drugs Work

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Combination therapy for cancer uses two or more treatments together to improve patient outcomes. This approach can extend life span and help protect vital organs and tissue from the damage that may come from using one treatment too much. It also attacks more than one cancer-causing pathway, which can lower the chance of treatment resistance. A clear example is the pair of acetazolamide and sulforaphane. Large tumors often have a low-oxygen, acidic center, and cancer cells respond by making...

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cancer-critical-genes-ii-tumor-suppressor-genes

How Tumor Suppressor Genes Prevent Cancer

Tumor suppressor genes help keep cell growth under control. They can slow cell division, repair DNA errors, or trigger apoptosis, which is programmed cell death. These jobs protect healthy cells and help maintain normal cell cycle progression. When a tumor suppressor gene is disrupted, cells can lose this control. Loss-of-function mutations in these genes can let damaged cells keep dividing. Over time, that unchecked growth can contribute to tumor formation and cancer. Most tumor suppressor...

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Retinoblastoma Gene and Childhood Eye Tumors

The retinoblastoma gene, or Rb, is a tumor suppressor gene linked to a rare eye cancer in children. Tumor suppressor genes are normal genes that help slow cell division, fix DNA mistakes, or trigger apoptosis, which is programmed cell death when damage cannot be repaired. These genes help protect the body from damaged cells growing out of control. Rb was the first tumor suppressor gene ever identified. It was discovered through study of retinoblastoma, one of the most common malignant tumors...

rous sarcoma virus (rsv) and cancer

How RSV Uses Src to Drive Tumor Growth

Rous sarcoma virus, or RSV, is a retrovirus that can trigger tumor growth in chickens. F. Peyton Rous first discovered it in 1911 as a filterable transmissible agent. His work showed that some cancers can be caused by infectious agents. He later received the Nobel Prize in 1966 for this discovery, which also helped lead to the finding of other cancer-causing viruses in animals and humans. RSV carries two copies of a plus-strand RNA genome. Its genome has four main open reading frames, or ORFs:...

key terms and concepts

Learn how cancer stem cells survive treatment, renew themselves, and help tumors return through resistance, recurrence, and metastasis.

How Cancer Stem Cells Drive Relapse | JoVE K12

molecular biology

JoVE Core Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

How Cancer Stem Cells Drive Relapse

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