By studying two forms of skin cancer, basal cell carcinoma and squamous cell carcinoma, researchers have discovered that the physical properties of the tissue from which the cancer originates may explain why some tumors are more likely to metastasize than others. .
- According to the researchers, the more benign basal cell carcinomas and squamous cell carcinomas do not have the same cellular environment, which may explain why some tumors metastasize and others do not.
- A stiffening of the basement membrane is an indicator of squamous cell carcinoma, while its softening would be more likely to indicate basal cell carcinoma.
How to explain that, faced with two initially similar skin cancers, one responds easily to treatment, while the other is aggressive and ends up metastasizing in other parts of the body.
A team of researchers from Rockefeller University in New York (USA) may have discovered why some tumors become more dangerous than others. In a study published in the journal Naturethey argue that it is the properties of the tissues surrounding premalignant tumor cells that strongly determine the aggressiveness of skin cancer.
Predict the evolution of a tumor by analyzing the basement membrane
To support this hypothesis, the researchers focused their work on two types of tumours: basal cell carcinomas, which are the most common form of skin cancer, and squamous cell carcinomas, a more aggressive form of skin cancer. The two types of tumors also have very distinct structures and appearances: basal cell carcinomas appear as bud-like clusters of cells, while squamous cell carcinomas begin as tiny folds in the skin tissue.
The scientists started by inducing each type of tumor in two different groups of genetically modified mice. They then measured their physical properties, as well as those of the surrounding tissues, and then built algorithms to simulate the appearance of tumours.
By analyzing the differences in gene expression between the two types of tumors, the researchers identified a set of genes that play an essential role in defining the physical properties of the basement membrane, i.e. the thin dense layer of intertwined proteins that is secreted by stem cells in the epidermis and by developing tumours. “The basement membrane acts as a sort of floor that separates the tumor from the surrounding tissue.”explains Vince Fiore, lead author of the study.
Using computer modelling, the team was able to see that softening the basement membrane or increasing the rate at which it is assembled would generate the characteristic buds of basal cell carcinomas. In contrast, stiffening the membrane or slowing its assembly rate would cause the folding associated with squamous cell carcinomas.
The researchers then tested these predictions by manipulating gene expression in rats. They turned out to be correct. “In each case, what we predicted actually happened.”says Professor Fiore.
A modification of the suprabasal cells
However, other experiments have shown that both types of carcinomas are not only shaped by the basement membrane. Their structure and behavior are also influenced by the stiffness of the so-called suprabasal cell layers, which lie directly above them.
Squamous cell carcinomas are characterized by a relatively stiff suprabasal “roof”, which makes it more likely that tumors will eventually break through the “floor” of the basal membrane, escape into deeper layers of skin and eventually metastasize throughout the body. Basal cell carcinomas, which have a less rigid suprabasal roof, are more likely to stay in place, making them more benign.
“Because epidermal stem cells make both the basement membrane and the underlying suprabasal cells, they control the architecture of the tissueanalyzes Professor Fuchs, co-author of the study. However, as stem cells acquire cancer-causing mutations that alter their gene expression program, they begin to lose control of the mechanical properties needed to keep the tissue fit and healthy.”
For the authors of the study, this work could in particular help clinicians to predict whether a tumor is likely to become aggressive, as well as develop new, earlier therapies.
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