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Cancer Stem Cells

© David Olle

What are stem cells?

Stem cells are immature, unspecialized cells that are capable of perpetuating themselves as stem cells and of undergoing differentiation into one or more specialized types of cells. Stem cells are most active during embryonic development, and give rise to all the tissues in the body. Adult stem cells are found in differentiated tissues and can differentiate to form all the cell types in the tissue from which they originated. Stem cells are most commonly found in the bone marrow, where they give rise to the different blood cells.

What are cancer stem cells?

The existence of cancer stem cells had been hypothesized for many decades, but was not until 1997 that they were isolated from patients with acute myeloid leukemia. 4 Subsequently, cancer stem cells have been isolated from breast 1 and brain cancers, and cancer cell lines. Cancer stem cells may derive from mutations in normal stem cells. Alternatively, differentiated tumor cells may acquire the characteristics of stem cells. Cancer stem cells are present in only very small numbers in tumors, and may not be present in all tumors.

The significance of cancer stem cells

Current therapies treat tumors as if all cancer cells had the ability to proliferate and metastasize. 5 Typically, the therapy shrinks the tumor and appears to be successful, but then the tumor grows back. The therapy killed the susceptible cells, but the resistant stem cells remained.

Stem cells have many of the characteristics of cancer cells. They share the ability for self-renewing cell division, and resistance to apoptosis (programmed cell death). Several of the molecular signaling pathways associated with normal stem cell development, such as Wnt, Shh and Notch, are also active in cancer development. Stem cells are notable for the presence of ATP-binding cassette transporters, which remove drugs from the cell. 3 Cancer stem cells maintain this characteristic, which accounts for the ineffectiveness of chemotherapy to destroy these cells. Normal stem cells are under tight metabolic control and divide only under specific conditions. Cancer stem cells no longer have these controls.

Chronic tissue injury as a cause of cancer

Chronic tissue injury can result from cigarette smoke, alcohol, stomach ulcers, acid reflux, inflammatory bowel disease, and other causes. These conditions result in a continuous need to replace damaged tissues. Stem cells are in a continuous state of cell division and signaling pathway activation that resembles the conditions seen in cancers. The inability to return to a quiescent state may result in the stem cell progressing to a cancer stem cell. 2