One of the most frequent forms of breast cancer, intraductal breast carcinoma (IDC) represents a commitment for Italian research to seek therapies tailored against carcinoma type.
This type of cancer in 30 percent of cases migrates from its site to affect other organs with metastasis , according to a molecular mechanism found and described in a study published in ‘Nature Materials’ by a team of researchers from the Firc Institute of the University of Milan , and supported by both Airc and the Cariplo Foundation and Miur
The Italian team’s result has made it possible to define a ‘mechanistic signature’ that could allow them to identify the types of neoplasms most at risk of producing metastases, so as to target them with ad hoc treatments.
Intraductal mammary carcinoma (IDC), according to the researchers, is 20% of the most prevalent type of cancer diagnoses, they explain, and is characterized by the occurrence of primary lesions within the mammary duct, which become immobilized due to severe compression by external tissue.
About 70% of the tumor remains ‘solid’ in situ, while the remainder can become fluid’ , managing to exit the breast.
Researcher Giorgio Scita, head of Ifom’s Cancer Cell Research Mechanisms Unit and full professor of General Pathology at State University explains that
“This characteristic makes this type of tumor an ideal model to study the relationship between state transition and the potential for metastasis.”
“Two years ago,” he recalls. we had found that Rab5A, a protein that regulates the ability of cells to internalize membranes and receptors, was surprisingly able to induce fluidization of a tissue of dense, packed epithelial cells. The action is reminiscent of that of a traffic warden who manages to make the congested traffic in our cities flow smoothly. What emerges from our laboratories today is that this motility, observed in a tumor model particularly sensitive to this factor, such as precisely intraductal breast carcinoma, is also associated with the ability of the tumor to modify the extracellular matrix and invade the surrounding tissue.”
“We engineered mammary gland cells in such a way as to elevate the level of Rab5A protein, typically highly expressed in the most aggressive breast cancers – report Andrea Palamidessi, Chiara Malinverno and Emanuela Frittoli, the first authors of the work – Thus, we observed that this simple manipulation is sufficient to reawaken the motility of a cell population that had gone into solidification and to allow the acquisition of smooth, flowing collective movements.”.
“The connection between the process regulated by Rab5 and the transition from a more solid state to a more fluid state,” Scita continued. – was explored further using an experimental system consisting of tumor spheroids immersed in a collagen matrix that mimics the microenvironment that our body typically develops to limit tumor growth. Taking advantage of genetic engineering techniques, advanced microscopy and biophysics, tumor cells were observed live to monitor its mode of movement and its ability to modify the collagen fiber network in order to generate channels and escape routes through which to invade the rest of the body.”
“In particular, to study the dynamic characteristics of the tissue and at the same time the forces that the spheroids exert on the matrix in 3D, we developed innovative models and algorithms for the quantitative analysis of the captured footage- point out Fabio Giavazzi, a researcher at Milan State University, and Roberto Cerbino, a professor of applied physics at the university, who also co-signed with Scita the first paper on the Rab5A protein (2017) – Crucial was the use of fluorescent markers that were dispersed in the matrix. It is by following their fluctuations that we were able to obtain information about the tensile forces exerted by the tumor masses on the matrix itself.”.
