The team of the biologist Ángela Nieto at the Institute of Neurosciences of Alicante (IN-CSIC-UMH), a mixed center of the CSIC and the Miguel Hernández University of Elche, is investigating one of the fundamental mechanisms of the cascade of metastatic reactions , the so-called epithelium-mesenchyme transition.
It is a process that plays an essential role in the development of the embryo , because it allows immobile epithelial cells to become mobile cells that can move to form the organs and tissues of the developing embryo.
These mobile cells are programmed to stop moving once they have fulfilled their role in the development of the embryo. Paradoxically, this mechanism, which is fundamental for the life of the embryo, can be very harmful if it is reactivated in adulthood, since it can facilitate tumor cells to spread and colonize other tissues and organs , where they can generate secondary tumors.
“We must continue to study primary tumors, especially cellular heterogeneity. The cells of a tumor are not all the same, they can even carry out different functions. And tumors evolve, acquire new mutations that modify their malignancy. But, in addition, now we must focus on the analysis of the metastatic niche : the environment in which cells disseminated by the activation of embryonic genes are going to colonize “, warns Nieto.
Until a few decades ago, the cancer arsenal was limited to surgery, chemotherapy, and radiation therapy. Today, there are more personalized and effective therapies : targeted, immunotherapy, hormone therapy, photodynamic and other advances, which have made treatments against malignant cells more selective.
With the new arsenal survival has increased. However, this achievement is overshadowed by the appearance of metastases , that is, the generation of secondary tumors, which are usually resistant to the treatments that ended the tumor from which they derive.
Even when the cancer may appear to have been defeated, some cells escaped from the initial tumor may have settled in other organs, hidden, invisible to the immune system. And it may take years for them to come forward. Although with a poor prognosis: 90 percent of cancer deaths are due to metastases. Hence, unraveling all its secrets is a priority.
“Metastasis is the key point in the approach to cancer”, points out Berta Casar, a CSIC researcher at the Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), in Santander. Trained at The Scripps Research Institute (United States), Casar leads a group that investigates the molecular processes that regulate the metastasis of melanoma (the most aggressive skin cancer), prostate cancer and pancreatic cancer.
Protein kinases play a key role in these processes, “which are a kind of internal cell messengers sensitive to external stimuli and which transmit signals to cells to initiate various activities in response,” the scientist summarizes.
Kinases are a type of protein involved in directing the response of cells to various stimuli, such as growth factors, cytokines, viruses or carcinogens. Above all, protein kinases regulate key functions of cells , such as proliferation, gene expression, differentiation, mitosis, cell survival, and programmed cell death, all of which are fundamental processes in the origin and evolution of cancer.
“In our group we use a multidisciplinary approach, which consists of the use of tumor lines, animal models and patient samples, to understand how the activation of protein kinases induces tumor progression and resistance to conventional therapies “, explains Casar. This type of protein could become a target for drugs in the treatment of metastasis.