The journey of tumor cells in the body obeys a series of complex mechanisms. The scientist Carlos López-Otín explains the ten keys to tumor processes, “the instruction book that cells must follow to transform themselves into selfish, mortal and traveling entities”
Carcinogenic cells. EFE/Rebeca Corcoles
Precisely “Selfish, mortal and traveler” (Editorial Paidós) is the title of the latest book by this biochemist and expert in the human genome, a journey to the heart of cancer that closes a trilogy on human vulnerability together with “Life in four letters” and «The dream of time».
In the chapter entitled “The essence of evil”, López-Otín tries to explain the complex processes of malignant cells based on the scientific and integrative vision of molecular oncologists Douglas Hanahan and Robert Weinberg who, first in the year 2000, and later in In 2011, they published scientific articles in “Cell” in which they described the characteristics of this journey to malignancy.
There are ten processes that cells follow to become malignant that do not keep a strict order, nor is there a specific time for each of them.
This general view of tumor processes opens the way to the development of new therapeutic strategies, now fundamentally based on one of them, the loss of control of cell proliferation.
“The future heralds the possibility of introducing alternative strategies aimed at intervening concomitantly on several of the distinctive properties of cancer that, as a whole, make up its true cellular and molecular essence”, affirms the also professor of the Oviedo University in his book.
The processes that tumor cells go through
1.- Autoactivation of cell proliferation: One of the characteristics of tumor cells is their ability to grow and divide without control and one of the reasons is that some of the signals that determine the time and rate at which they should proliferate are altered.
two.- Insensitivity to cell growth inhibitors: But not all cells are capable of endless proliferation. To try to avoid it, biological evolution itself endowed the human being with a series of genes encoded for cell growth inhibitors.
“Among the genes that put pause and calm in the life of cells, two stand out, TP53 and RB”, but in tumor cells both are usually inactivated and proliferative chaos manages to prevail, explains the author.
3. Resistance to apoptosis: But the growth of tumors does not depend only on the rate of cell division, but also on the rate of cell death, which is called apoptosis.
Proteins are activated that help destroy damaged cells and thus prevent them from dividing further. But the journey on the part of these malignant cells continues to develop various strategies that free them from death, from apoptosis.
4.- Acquisition of replicative immortality: The path towards immortality of tumor cells, which began with the evasion of cell death mechanisms (apoptosis), is completed with the activation of a strategy that ignores the limit that indicates the maximum number of divisions that can undergo normal cells. They then reactivate telomerese, an enzyme with which they manage to jump that barrier and reach a state of replicative immortality that allows them to divide endlessly.
5.- Induction of angiogenesis: The process of formation of new blood vessels from existing vessels is known as angiogenesis and is essential for feeding the primary tumor and also metastases.
6.- Stimulation of invasion and metastasis mechanisms: Some cells of the primary tumor acquire additional mutations that allow them to invade the surrounding tissue, spread and colonize other territories to generate metastases. The journey begins with local invasion, passing through blood or lymphatic vessels and traveling to other distant tissues or organs. There, small nodules or micrometastasis are formed, the processes of angiogenesis (feeding) and colonization begin until a clinically detectable macrometastasis is generated.
7.- Reprogramming of energy metabolism: Tumor cells are metabolically reprogrammed to simultaneously guarantee the supply of energy and that of certain metabolic precursors. “This gives them a notable advantage over normal cells and allows them to continue growing and evolving to face the next stages of their progression,” explains López-Otín.
8.- They escape the immune system: The immune system tries to unmask the tumor cells that hide among the normal ones and activates innate immunity and adaptive immunity to eliminate them. But malignant cells develop immunomodulatory proteins that slow down the activity of the immune system that keeps them under control, as if asleep, for months or years until they wake up due to their tireless adaptive capacity or due to defects in the immune system caused, for example , by the passage of time or by situations such as stress.
9.- Chronic inflamation: The cells of the immune system are responsible for eliminating pre-tumor or tumor cells, a process that has a “dark side” by generating a chronic inflammatory response that favors all stages of tumor development. But it’s also common for inflammation caused by a variety of factors—from viral or bacterial infections to obesity—to contribute to cancer risk.
10. Genomic instability: If tumor cells did not acquire a state of genomic instability that promotes the rapid accumulation of mutations, cancer could not develop in most cases. Normal cells have mechanisms to avoid this instability (from the arrest of cell division to the repair of genetic material or cell death).
But tumor cells deactivate such mechanisms and a genomic instability is produced that stimulates the progression of cancer in this “selfish” and “wandering” journey, explains Dr. López-Otín.
