Tumor cell escape from therapy-induced senescence.
Tareq Saleh1, Liliya Tyutyunyk-Massey1, Graeme F Murray2
1Departments of Pharmacology & Toxicology and Medicine, and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States.
Biochemical Pharmacology
|December 22, 2018
Summary
Certain cancer cells can recover from chemotherapy-induced senescence, regaining self-renewal capacity and forming tumors. This suggests that senescence may not always be a terminal state, potentially contributing to disease recurrence.
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- Chemotherapy often induces cellular senescence, a state of irreversible growth arrest.
- Senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells.
- The long-term fate and proliferative potential of chemotherapy-induced senescent cells remain incompletely understood.
Purpose of the Study:
- To investigate the proliferative capacity and tumor-forming potential of chemotherapy-induced senescent cancer cells.
- To determine if senescence represents a terminal growth arrest in specific cancer cell lines.
- To analyze the dynamics of the Senescence-Associated Secretory Phenotype (SASP) during recovery from senescence.
Main Methods:
- Induction of senescence in H460 (lung), HCT116 (colon), and 4T1 (breast) cancer cell lines using etoposide or doxorubicin.
- Enrichment of senescence-like cells using flow cytometry based on β-galactosidase staining, cell size, and BTG1-RFP reporter.
- Assessment of proliferative capacity using mass culture, real-time microscopy, and High-Speed Live-Cell Interferometry (HSLCI).
- Tumorigenicity assays in immunodeficient and immunocompetent mice.
Main Results:
- Chemotherapy-induced senescent cancer cells recovered proliferative capacity in vitro.
- Recovery was observed in both bulk cultures and enriched populations of senescent-like cells.
- Senescence recovery was associated with attenuation of the Senescence-Associated Secretory Phenotype (SASP).
- Enriched senescent-like cells formed tumors in vivo in both immunodeficient and immunocompetent hosts.
Conclusions:
- Chemotherapy-induced senescence may not always be a terminal state of growth arrest.
- Recovered senescent cells possess self-renewal capacity and can form tumors.
- These findings suggest a potential mechanism for cancer recurrence after chemotherapy.
- Further research is needed to understand the clinical implications of reversible senescence in cancer treatment.
Related Concept Videos
02:15Replicative Cell Senescence
4.4K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.4K
01:26Escape Velocity
8.4K
The escape velocity of an object is defined as the minimum initial velocity that it requires to escape the surface of another object to which it is gravitationally bound and never to return. For example, what would be the minimum velocity at which a satellite should be launched from the Earth's surface such that it just escapes the Earth's gravitational field?
To calculate the escape velocity, it is assumed that no energy is lost to any frictional forces. In practice, a satellite...
To calculate the escape velocity, it is assumed that no energy is lost to any frictional forces. In practice, a satellite...
8.4K
01:19Escape Velocities of Gases
1.4K
To escape the Earth's gravity, an object near the top of the atmosphere at an altitude of 100 km must travel away from Earth at 11.1 km/s. This speed is called the escape velocity. The temperature at which gas molecules attain the rms speed, which is equal to the escape velocity, can be estimated by using the equation for the average kinetic energy of the gas molecules. According to the kinetic theory of gas, the average kinetic energy of the gas molecules is proportional to its...
1.4K
00:59Gene Therapy
27.6K
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
27.6K
01:13Induced Pluripotent Stem Cells
28.0K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
28.0K
01:21Stem Cell Therapy for Tissue Regeneration
4.7K
Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
4.7K