On a study on tumor cells, a group of researchers from the Federal University of São Paulo (Unifesp) is trying to find out why certain proteins, which should be found in the nucleus, end up in different places. Among the locations, they are even outside the cell. The phenomenon, which was not expected, may indicate a relevant pattern for the purposes of diagnosis and prognosis of various types of cancer.
The results already obtained were published on the cover of the scientific journal Traffic. Researchers Juliana A. de Morais and André Zelanis, from the Laboratory of Functional Proteomics at the Institute of Science and Technology (ICT-Unifesp), reanalyzed public data in international repositories by scientists from different countries. According to Zelanis, a fraction of the cells can be sent abroad.
“Proteins are produced and addressed to different points within the cell. And there is a fraction of them that are sent out of the cell, to perform some function in its surroundings, such as forming an extracellular matrix. The proteins follow a defined route of secretion, what we call the canonical route. Proteins that are destined to go outside the cell, for example, have signals that tell it this route of secretion.”
Thus, when it comes to tumor cells, there is usually a certain genomic instability, in addition to an accumulation of mutations in genes. These regulate cell growth and proliferation. Thus, there are several metabolic processes that can be deregulated. Among them is the secretion of proteins.
The first step of the study ended up being the capture, in public repositories, of raw data on cells from breast, melanoma, ovarian, colon and Ewing sarcoma tumors (a rare cancer that usually affects children, adolescents and young adults). Some proteins had the cell nucleus as their destination, but took a non-canonical route and were secreted “improperly”. This pattern was observed in all types of tumor cells analyzed.
In the initial group, 6,092 proteins were idenfied, where 28% adopted non-canonical routes. Thus, they were secreted to different places than expected. Altogether, 19 are present in all types of cells analyzed and were observed in the cytoplasm, even if they did not have functions associated with the nucleus.
“We then went to see if histologically there was any record showing that these proteins, in the tumor situation, were in a different location, which was observed in part of the 19 proteins. This is another independent observation that supports our results.”
Now, researchers are already planning the next steps to seek the answers. In this way, they will select proteins and investigate their biological role in different types of cancer, starting with functional studies. Initially, Morais and Zelanis should study more about melanoma.
“Our study has so far analyzed proteins from databases of secretome cells in culture. Only one of the samples came from a patient’s cell. Now we want to study plasma samples from melanoma patients to find these proteins, look for markers. validation of everything we’ve discovered so far in samples from patients with and without cancer so that we can compare and see if it’s a process that only occurs in tumor cells.”