38.15
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 c…
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 tumor and sustain its growth.
This heterogeneity in the cancer cell population makes it difficult for most cancer therapies to target and get rid of all cancer cells at once.
Moreover, cancer stem cells use survival mechanisms such as increased activation of drug efflux pumps, DNA repair activity, or the expression of detoxification enzymes that help them escape the cancer therapies.
For example, the anticancer drug - imatinib mesylate is frequently used in the treatment of chronic myeloid leukemia. While differentiated cancer cells are sensitive to the drug, cancer stem cells can escape the therapy by exhibiting over-expression of the ABCB1 and ABCG2 membrane transporter proteins.
These proteins help the cells to efflux the drug and reduce its intracellular levels, leading to the generation of resistant cancer cells.
A single surviving cancer stem cell can reestablish the culture, resurrect the disease, and cause tumor relapse.
View the full transcript and gain access to JoVE Core videos
Q1: What are cancer stem cells and how do they differ from regular tumor cells?
Cancer stem cells are a small population of cells within tumors capable of self-renewal and differentiation into multiple cell types. Unlike regular tumor cells, cancer stem cells possess the ability to generate new tumors and maintain long-term tumor growth. They exhibit properties similar to normal stem cells but operate within the malignant context of cancer progression.
Q2: How do cancer stem cells contribute to tumor maintenance?
Cancer stem cells sustain tumors through continuous self-renewal, producing both new cancer stem cells and differentiated progeny that form the bulk of the tumor. This hierarchical organization allows tumors to persist and grow over time. Their resistance to conventional therapies makes them critical drivers of tumor maintenance and recurrence.
Q3: What mechanisms allow cancer stem cells to resist treatment?
Cancer stem cells employ multiple resistance mechanisms including slow proliferation rates, enhanced DNA repair capacity, and expression of drug efflux pumps that expel chemotherapy agents. Their quiescent state and protective niche interactions further shield them from conventional treatments. These properties make targeting cancer stem cells essential for improving therapeutic outcomes.
Q4: What role does the tumor microenvironment play in supporting cancer stem cells?
The tumor microenvironment provides a protective niche that sustains cancer stem cell function through cellular and molecular interactions. Stromal cells, immune cells, and extracellular matrix components create conditions favoring self-renewal and survival. This supportive environment helps cancer stem cells evade immune detection and maintain their stemness properties.
Q5: How can cancer stem cells be identified in laboratory and clinical settings?
Cancer stem cells are identified using markers such as surface proteins, aldehyde dehydrogenase activity, and functional assays like sphere formation and serial transplantation. Flow cytometry and immunohistochemistry detect specific marker combinations characteristic of cancer stem cells. Functional assays demonstrating self-renewal capacity provide the most definitive identification.
Q6: Why are cancer stem cells considered important therapeutic targets?
Cancer stem cells are therapeutic targets because eliminating them could prevent tumor recurrence and improve long-term survival outcomes. Their role in maintaining tumors and driving progression makes them critical for developing more effective cancer treatments. Targeting cancer stem cells alongside bulk tumor cells represents a promising strategy for improving cancer therapy efficacy.