The "Switch" for Cancer
No "glue" between cells that are still benign - this ultimately allows malignant carcinomas to develop: Scientists have succeeded in proving that the loss of certain molecules on the surface of cells drives the latter to become malignant. This is not the consequence, but the cause of the development of carcinomas. "The current observations mean the first direct proof of a causal role of E-cadherin in the development of benign adenomas into malignant carcinomas in the organism," reports Anne-Karina Perl from the Institute for Molecular Pathology (IMP) in Vienna together with her co- Authors in Nature.
Malignant tumors are characterized by their limitless growth and invasion of surrounding tissue areas. The scientists: "In part, the development of malignant tumors is characterized by their ability to overcome cell adhesion and invade adjacent tissue."
This normal binding mechanism of benign cells is ensured by molecules on their surface. To hold them together, they stick to each other via such E-cadherin components.
The highlight of the work of the Viennese scientists: they studied the critical transition from (still) benign tumors – so-called adenomas – to malignant carcinomas in mice. Although the former grow, they do not spread uncontrollably into the tissue and do not set secondary tumors (metastases). If the cohesion is lost, they develop into carcinomas.
This is done by eliminating the "cell glue" E-cadherin. The scientists: "Restoring the normal function of cadherin in tumor cells reverses the development." The aggressive malignant cells become benign again.
Up until now, however, the question has been whether the loss of E-cadherin is the result or the cause of the development of carcinomas. The scientists investigated this in transgenic mice.
For example, laboratory mice from a certain strain (Rip1Tag2) have a high risk of developing pancreatic cancer. These animals were crossed with laboratory mice, which have the ability to continue producing the "glue" that keeps cells connected despite such tumors.
According to the scientists, this was a definite "tumour brake". The development of adenomas towards malignant carcinomas was "arrested" at the benign stage. Conversely, the researchers proved that crossing the carcinoma mice with animals that had an insufficient form of "glue" led to the rapid development of pancreatic cancer and very soon to the formation of metastases.
The work of the Viennese scientists is so important because many malignant carcinomas have so-called adenomas as – initially – harmless precursors. Carcinomas develop from degenerated epithelial cells. The latter cover inner or outer surfaces of the body as a separating layer. If these cells degenerate, one speaks of carcinomas. This includes the most common cancers such as lung, stomach, colon, breast, prostate, pancreas and other cancers.