Madrid, June 3 (Europe Press) –
Researchers at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) and the University of Cambridge in the United Kingdom have developed an innovative mouse genetic model that allows the discovery of the initial steps that lead to the development of cancer. This multi-colored label system called “Red2Onco” makes it possible to track intestinal tumor progression after the first carcinogenic effect at the single-cell level, as published in the journal Nature.
Cancer studies are limited to the extent that cellular transformations are clinically detectable. However, the initial stage on the course of the malignancy is not histologically visible, since the process arises from a single cell.
In this initial stage, the so-called ‘sorted cell’ acquires a first lethal mutation, also known as ‘first genetic hit’, while being completely surrounded by normal tissue. To overcome the detection barrier, a team of researchers around IMBA group leader Bon-Kyoung Koo and Cambridge University group leader Professor Benjamin D. Simons has developed a new screening system.lab to dissect precancerous pathways that have so far remained under the radar.
“With the advancement of technologies such as deep DNA sequencing, researchers have realized that cancer-related mutations are already present in normal tissues, which is very scary,” says Boon Kyung Koo, referring to the tipping point that put him, like a forensic investigator, in the footsteps of his first infection. carcinogenic;
Since most human cancers originate in the epithelium, Koo decided to build a genetic model to examine the impact of early neoplastic transformations in the mouse gut. This gene model, which the team dubbed “Red2Onco,” is a multicolor labeling technology that allows tracking of the onset of tumors from a single mutant cell.
Using ‘Red2Onco’ the team discovered that the mutated cells create a hostile environment for neighboring non-mutated cells and significantly liberate the niche of normal stem cells in the mice’s gut tissue. “This is by far the most exciting technique we’ve tried,” says Bun Kyung Ko
Thanks to ‘Red2Onco’, the team was able to study the mechanisms initiated by various ‘preliminary carcinogenic findings’. These are mutations in the known primary oncogenes, KRAS and PI3K, respectively, which are known as carcinogenic factors that lead to malignancy in overt tumors.
To their surprise, the researchers discovered that even in the case of first successful tumorigenesis, the cancerous mutant cell or “sorted cell” exerts a “negative effect” on its neighbors. The surrounding normal tissues lose stem cells, which in turn favors the regional expansion of mutant CSCs and their offspring.
“Through this ‘field transformation’ process, colonization of intestinal tissue by mutant cells increases the potential for new tumorigenic successes, which can lead to cancer,” explains Benjamin Simmons of the University of Cambridge’s Gordon Institute.
The study’s first author, Min Kyu Yum from the Gurdon Institute, adds that “neoplastic mutant cells influence the fate behavior of their wild-type neighbors directly, through the secretion of signaling factors, and indirectly through induced changes in the common tissue environment.”
For his part, co-first author Seungmin Han notes that “using comparative analyzes of single cells and OA methods, it has been possible to dissect the molecular mechanisms mediating cell interference.”
The authors showed that inhibiting BMP (bone morphogenetic protein) signaling from the neoplastic mutation attenuates the ‘negative effect’ on normal stem cells. Min Kyu-Yom concludes, “In addition to allowing the detection of early oncogenic events, our finding opens the way for intervention strategies targeting cellular crosstalk mechanisms.”