According to the American National Institute of Health (NIH) a tumor is defined as an abnormal mass of tissue that appears when cells multiply more than expected or do not die when they should. When these cells acquire the ability to grow beyond their usual boundaries to invade adjoining parts of the body and/or spread to other organs, then it is classified as cancer1,2.

In healthy tissues cells can divide a certain number of times before dying. Tissue maintenance and cell renewal is possible thanks to the existence of very special cells called stem cells. These stem cells can give rise to any kind of cell in a process called differentiation. Whereas regular tissue cells divide into two identical daughter cells, stem cells suffer a process called asymmetric division that results in a new stem cell and a tissue-specific cell, which is scientifically recognized as a “differentiated cell”. This process is represented in the figure below and it allows the maintenance in each tissue of a subset of cells able to give rise to all the cell-types in that tissue. Let’s see that with a couple of examples. Our skin is formed by three main layers. The outermost layer of the skin is the epidermis and it is organized, for its part, in many other layers of cells named mainly keratinocytes. On the surface of the skin are the oldest cells, those that will die soon and detach from the surface as the so-called dead skin. The renewal of keratinocytes is possible thanks to the stem cells placed in the deepest layer of the epidermis which generate new keratinocytes when they are needed that grow to the upper layers as they mature. However, stem cells have also the ability to activate and divide when there is a high demand of new cells. For instance, when we get our skin injured, stem cells activate and give rise to new keratinocytes that populate and heal the wound.

Thereby, stem cells are the major directors of tissue maintenance and growth. Similarly, in the late XXth Century it was proposed that a subset of cancer cells could act as stem cells and maintain a self-renewal ability that ensures the maintenance of tumors over the time3. This hypothesis was based on the observation of a subset of cancer cells that showed differing growth characteristics and colony morphology. These cells would characterize by being less proliferative than normal cancer cells and start to asymmetrically divide whenever there are new cells requirements.

During the following years, a lot of efforts were made to identify and characterize these Cancer Stem Cells in different tumor types. Today, Cancer Stem Cells with tumor-specific hallmarks have been identified in almost all of them.

Cancer stem cells are responsible for tumor treatment surveillance

Most of the traditional cancer treatments are designed to act on actively proliferative cells, which is a well-known feature of cancer cells. However, Cancer Stem Cells are not so proliferative. Thereby, it is thought that these cells are able to survive traditional chemotherapy and remain dormant for a period of time. Afterwards, cancer stem cells can activate and initiate again tumor growth giving rise to a relapse.

As we mentioned before, the main difference between cancer and a benign tumor is the ability of the first one to spread to adjacent or distant tissues. It is thought that metastasis occurs when a Cancer Stem Cell travels to a new organ where it remains, and the growth of a new tumor starts.

Future directions

It is clear that cancer is, nowadays, one of the major public health problems worldwide. Despite the pandemic has captured most of our attention in the last two years, cancer cases are still rising and unfortunately cancer deaths are also increasing year by year. Therefore, designing new treatment methods able to act specifically on cancer stem cells is a major challenge in this era.

As the features and behavior of Cancer Stem Cells are described, many research groups are working on the development of new treatments and tools that will help with the identification and managing of these aggressive tumor cells. Combining treatments that act both on tumor cells and cancer stem cells will be a very effective approach not only to tumor elimination but also to the prevention of tumor metastasis and relapse.

Our diagnosis platform QF-Pro® could help to identify these cells in tumor biopsies and be an efficient tool for the precision and effectiveness of new cancer treatments.

REFERENCES

  1. National Institute of Health. National Cancer Institute. LINK
  2. World Health Organization. LINK
  3. Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells. Science. 1977;197(4302):461-3.