A discovery by the Transformation and Metastasis Group of the Spanish National Cancer Research Centre (CNIO), along with IDIBELL, opens a path towards the identification of precancerous breast lesions that will develop into tumours. This work, directed by Eva González-Suárez, is published in the scientific journal Nature Communications.
The research has focused on the role of the RANK protein, whose intervention in the genesis of breast tumours was discovered by González-Suárez herself in 2010 at the Bellvitge Biomedical Research Institute (IDIBELL), where she maintains a line of clinical research.
Two types of cells coexist in breast tissue: luminal cells, which produce milk; and basal cells, which are contractile and allow the expulsion of that milk. Several studies suggested that breast tumors originate exclusively in a subpopulation of luminal cells, the so-called luminal progenitors.
The work that is now being published, with Jaime Redondo-Pedraza as first author, reveals instead that tumours can start in other types of cells, which the authors call “unfaithful” cells and which derive from basal cells.
The ‘unfaithful’ cells in which cancer begins
The new research shows that the expression of the RANK protein in basal cells causes them to lose their identity and become new cells that are clearly neither basal nor luminal, but hybrid, with characteristics of both. These are the unfaithful cells.
All types of breast tumors, both luminal tumors, would begin in unfaithful cells. Those that express hormone receptors (+), and also “triple negative” tumors that do not express them (-).
“What we know now is that basal cells in the breast can give rise to all types of tumours,” explains Eva González, researcher at the CNIO and leader of the Transformation and Metastasis group at IDIBELL. “We could say that the defined identity of the cells protects against the appearance of tumors. However, when cells lose their initial identity and become those hybrid or unfaithful cells, wherever they come from, that’s when they give rise to the appearance of cancer.”
Genetic signature in lesions that will progress to cancer
The group has developed a genetic signature, which detects these unfaithful cells at the origin of precancerous lesions. This would allow the identification of which of them are going to evolve into invasive tumours.
After their work identifying the genetic signature in mice, Eva González-Suárez’s group has tested this new marker with a cohort of human breast precancerous lesions and has found that it can effectively identify those lesions that will become cancer.
“A common diagnosis in the breast is that of ductal carcinoma in situ, a lesion considered precancerous for which until now it was not possible to know whether or not it was going to evolve into cancer,” says González-Suárez. “Since that could not be known until now, all women who are diagnosed with these lesions are treated as if it were already cancer. In other words, a very high number of women are being overtreated.”
Diagnoses of these precancerous lesions have increased thanks to screening programs and improved imaging techniques, to the point that, right now, 20% of all cancer diagnoses are those precancerous lesions that are not actually cancer. Of these, only 30% will become cancer, but the impossibility of knowing which ones has meant that the vast majority are treated as cancers.
The genetic signature identified by Eva González’s group could detect precancerous lesions that are going to evolve into invasive tumours, that is, into cancer.
“Now we have to confirm the signature with an independent cohort and refine it so that it can be used in the clinic to identify the lesions that will become invasive cancer,” says González.
About the Spanish National Cancer Research Centre (CNIO)
The Spanish National Cancer Research Centre (CNIO) is a public research centre under the Ministry of Science, Innovation and Universities. It is the largest cancer research centre in Spain and one of the most important in Europe. It integrates half a thousand scientists, plus support staff, who work to improve the prevention, diagnosis and treatment of cancer.
About IDIBELL
The Bellvitge Biomedical Research Institute (IDIBELL) is a research centre created in 2004 specialising in cancer, neuroscience, translational medicine and regenerative medicine. It has a team of more than 1,500 professionals who, from the 73 research groups, generate more than 1,400 scientific articles per year. IDIBELL is owned by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centres accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Centre of the AECC Scientific Foundation (FCAECC).
Funding bodies: European Research Council (ERC); Autonomous Community of Madrid; “la Caixa” Foundation, Ministry of Science, Innovation and Universities through the State Research Agency.