Stem cells could be a key factor in cancer

One day in the not too distant future, stem cells could help repair diseased tissue and may become a therapeutic tool of excellence to treat Alzheimer’s disease, diabetes, hepatitis and Parkinson’s disease. However, there is a more pressing reason to study stem cells: some types of cancer are known to originate from these cells and they may even be the root cause of all cancers. This is the focus of discussion in the IV Barcelona BioMed Conference entitled "Stem Cells and Cancer", held from Monday to Wednesday and hosted by the Institut d’Estudis Catalans (IEC). This conference has brought together twenty leading scientists in a field of study that may revolutionize therapeutic treatments used in the fight against cancer. The 150 conference attendees are addressing two key issues: firstly, the similarities between healthy and cancer stem cells and, secondly, how the latter cell type can be identified and characterized.

The working hypothesis of the scientists is that at the heart of every tumor is a handful of malignant cells with stem cell properties, referred to as cancer stem cells, that cause the onset of cancer and its spread. The unlimited dividing capacity of stem cells ensures constant replenishment of healthy tissue. However, this same capacity favors tumorigenesis by stem cells that have undergone cancerous mutations. In addition, cancer stem cells may show more resistance to chemotherapy, which would account for the difficulty to completely remove tumors and also the eventual onset of metastasis. According to Joan Massagué, adjunct director of IRB Barcelona, member of the IEC and chairman of the Cancer Biology and Genetics Programme of the Memorial Sloan Kettering Cancer Center in New York, "during metastasis a few cells that escape from the primary tumor have the capacity to re-initiate tumor growth after invading distant vital organs. Therefore, we believe that it is during metastasis that the tumor must resort to its "stem cell" capacity. In fact, we are close to identifying genes that confer this capacity during breast cancer metastasis". The researchers at IRB Barcelona’s Metastasis Laboratory are studying the process of metastasis in breast and lung cancer. The objective is to identify "stem cell" and other functions that allow these kinds of tumors to metastasize.

Discovery of cancer stem cells

Cancer stem cells were first found in the blood, especially in some kinds of leukemia, and were subsequently identified in solid tumors such as in the breast, brain, lung and colon. Hans Clevers and Eduard Batlle, researchers in cancer stem cells in colorectal cancer at the Hubrecht Laboratory in the Netherlands and IRB Barcelona respectively, and co-organizers of the conference, explain that "in less than 5 years remarkable results have been achieved that indicate that, in certain types of tumor, there is a kind of hierarchy of cancer cells, the most dangerous being those that acquire "stem cell" functions. John E. Dick, invited speaker at the BioMed Conference, first reported these cancer cells in several types of leukemia and has recently published an article about how to identify cancer stem cells in colon cancer.

A new strategy to fight cancer

The hypothesis also points towards a new strategy to fight cancer. Current drugs attack the mass of the tumor and shrink it considerably; however, they are ineffective against this evasive group of cells. This is explained by the fact that current pharmaceutical agents used in chemotherapy intervene in cell division and, while ordinary tumor cells divide rapidly, the “stem” cells divide more slowly and therefore escape the action of these drugs. However, to develop or select new drugs it is first necessary to identify cancer stem cells and above all distinguish them from healthy ones.

Basic questions about stem cells and cancer

What are stem cells?

Stem cells have unlimited capacity for self-renewal, and in certain conditions can generate any tissue or organ in the human body. When a stem cell divides, of the two resulting cells one maintains the characteristics of the stem cell while the other becomes tissue-specific. The most important feature of stem cells is their capacity to self-renew in order to maintain the cell population. These cells have an unlimited lifespan and proliferation potential.

There are two types of stem cell: embryonic and adult.

Embryonic stem cells are found in the inner cell mass of an embryo in the first two weeks of life (7-14 days), after which they disappear. These cells are pluripotent, that is to say they can differentiate into any type of cell in the body. It is precisely the embryonic origin of these cells that generates controversy, both ethical and moral, regarding their use.

Adult stem cells derive from adult tissues and have been found in bone marrow, spinal cord, brain, muscle, stomach, breast, and in many other tissues and organs. These cells are multipotent, meaning that they can generate all the cell types of the organ/tissue from which they originate. For example, blood stem cells can produce all cell types found in blood, such as red blood cells, white blood cells and platelets.

What are cancer stem cells?

This is the name given to tumor cells that have acquired stem cell properties, such as unlimited dividing capacity. The working hypothesis of researchers is that each tumor contains a core of cancer stem cells which ensures its perpetuation, growth and regeneration.

When did scientists discover that stem cells could be involved in cancer?

This notion, which is not new, came about from the observation that both tumor cells and stem cells show this extensive capacity to divide and proliferate. However, there was no evidence to support this hypothesis until five years ago when researchers began to observe what they called markers, namely stem cell surface molecules, which were also found in some kinds of tumor cells.

What kinds of cancer appear to derive from these cells?

It is possible that all tumors derive from this small group of cancerous stem cells. To date, they have been detected in several kinds of leukemia and in some solid tumors, such as breast, brain, lung and colon cancer.

How can this finding contribute to new treatments?

If this hypothesis is confirmed, it will undoubtedly lead to new treatments. To date, all anti-cancer agents have been chosen on the basis of their capacity to shrink tumors, which implies that they kill ordinary cells that comprise the tumor mass - but often the tumor regenerates.

In the case of cancer stem cells, regeneration occurs because the drugs do not kill the cells from which the cancer originates. This suggests that a new strategy for the selection of anti-cancer drugs is required as well as the discovery of pharmaceutical agents that can eradicate cancer stem cells. The challenge lies in identifying clear therapeutic targets that differentiate normal stem cells from cancer ones.