Stem Cell Research Advances Cancer Knowledge

Cancer researchers are discovering that at least some tumors arise from cancer stem cells that share characteristics with other kinds of stem cells.

What are stem cells? They are cells inside us that can divide and renew themselves throughout life. Stem cells have an unrivaled capacity to drive and shape growth by proliferating through repeated cycles of cell division.

Embryonic stem cells arise within days of conception inside a microscopic, still-round embryo, and they can give rise to any kind of cell within the organism — a potential researchers call “pluripotency.” In adults, stem cells are rare and different from most other cells.

Most other cells in adults have reached a terminal stage of development. They are specialized — “differentiated” — meaning they perform just one defined set of tasks. They rarely, if ever, divide to generate new cells. They may wear out and eventually die.

Stem cells do not normally wear out and are essentially immortal. They never commit to a final development into a specialized cell.

When tumor cells from patients are separated from one another and given a chance to grow in a laboratory culture dish, only a very small percentage of the tumor cells are capable of regenerating the tumor. Some researchers believe these are the cancer stem cells.

Cancer stem cells now are thought to be the originators of many tumors. Furthermore, some scientists suspect that cancer stem cells may prove to be the cells most responsible for resistance to current drugs used to treat cancer. Gaining a better understanding of the molecular, biochemical and functional characteristics of cancer stem cells may lead to the development of more effective, precisely targeted treatments. Drugs that target the majority of cancer cells that cannot self-renew are not likely to be effective. On the other hand, drugs that target only the tiny proportion of cancer cells with self-renewing properties are most likely to have long-term benefit. But there is still much to learn.

Where Do Cancer Stem Cells Come from?
Cancer stem cells, like other stem cells, are essentially immortal — they can divide indefinitely, renewing themselves and spinning off daughter cells. However, unlike the stem cells that shape normal development, cancerous cells grow uncontrollably.

Some researchers suspect that cancer stem cells arise from adult stem cells that go awry. Compared with embryonic stem cells, adult stem cells are much more limited in the types of cells they can spin off. But unlike the bulk of fully specialized, or “differentiated,” tissue cells, adult stem cells can keep dividing. In so doing, they renew themselves and engender progenitor cells that in turn give rise to specialized cells.

The best known adult stem cells are those that give rise to red and white blood cells and platelets that aid clotting. After a bone marrow transplant, these “hematopoietic” stem cells regenerate the blood system of the bone marrow recipient. But researchers also have begun to discover rare stem cells in other adult tissues.

While several researchers are investigating the likelihood that some tumors get their stem cell characteristics from stem cells themselves, others are looking into the possibility that cancer stem cells might acquire their characteristics another way. Scientists are investigating whether progenitor or even fully differentiated cells somehow shirk assigned roles, de-differentiate and acquire stem-cell-like potency en route to becoming cancerous.

Development and Cancer
Cancers that arise in different tissues often acquire similar genetic abnormalities. Even so, developmental programs vary for cells in different tissues, and may differently shape the characteristics of tumors that emerge within those tissues. To better understand cancers and cancer stem cells — and to discover new weaknesses in cancers to attack with new drugs — researchers believe it is important to learn more about how the properties of stem cells are determined in tissues at different stages of development, and to learn how combinations of genes that become abnormal in cancer might act differently in undifferentiated stem cells, differentiated cells and various tissues.

In some cases, researchers have been able to separate individual cells from embryos and grow them into a population of embryonic stem cells that can replicate continually in the laboratory. Also useful are cell lineages created by injecting DNA from an adult cell into an unfertilized egg cell from which the nucleus has been removed. This procedure, called somatic cell nuclear transfer, has been used to clone animals, most famously Dolly the sheep.

Human reproductive cloning — cloning humans — is unsafe and unethical. Therapeutic cloning to regenerate damaged tissue — for instance, heart muscle after a heart attack or beta cells of the pancreas in diabetes — is a major clinical goal. But at a molecular level of detail, stem cell researchers also have a wealth of knowledge to gain about the fundamental biology of development — about how and why cells at a particular time and location within the organism retain or lose the capacity to survive or replicate, and either remain uncommitted or become fated to a specific role in a particular tissue. The same questions are important to investigate in cancer.

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