Researchers from Unifesp have identified a protein that promotes the survival of tumor cells outside their original tissue. In laboratory conditions, by blocking SDC4, scientists were able to reduce mechanisms associated with metastasis and uncontrolled cell proliferation.
This finding, published by Agência FAPESP, opens a new avenue for studying cancer, although additional trials are required for patient application.
Syndecan-4 (SDC4) is located on the surface of cells and is usually involved in their attachment to tissues. The problem arises when this molecular component is overexpressed, which is linked to the development of tumors. The team at the Federal State University of São Paulo (Unifesp) found that this protein acts as a kind of protection for more aggressive cancer cells.
By suppressing SDC4 activity, researchers managed to reduce the ability of these cells to remain alive after detaching from the tissue. This process is directly related to metastasis—the spread of malignant cells throughout the body and the formation of new disease foci. The study indicates that SDC4 could become a promising therapeutic target and a marker for monitoring tumor progression. The strategy of suppressing this molecule potentially has the capacity to halt the proliferation of cancer cells.
Carla Cristina Lopes, a professor at the Department of Biological Sciences at Unifesp and corresponding author of the article, noted that the research is 'in its initial stages' and requires further verification of the results.
In the experiments, scientists analyzed rabbit endothelial cells in the laboratory. The cells were placed in conditions where they could not attach to the surface, mimicking the state of tumor cells during systemic spread. Most of them did not survive, but a smaller group survived this stress and began producing high levels of SDC4. When researchers disabled the production of this protein using genetic engineering methods, these cells lost characteristics associated with cancer and once again became dependent on tissue attachment for survival.
The main observed effects after blocking SDC4 included: increased production of the p27 molecule, which slows cell division; reduced invasive capacity of the cells; restoration of the balance between cyclin proteins and CDK; and decreased survival of cells resistant to natural death.
The study touches upon the phenomenon of anoikis—a natural mechanism of cellular elimination that occurs when a cell loses contact with tissue. Aggressive tumor cells are capable of avoiding this process, which contributes to the formation of metastases. Lopes emphasized that 'syndecan-4 protects tumor cells from this specific type of cell death that occurs when a cell detaches from tissue.'
The results still need to be confirmed in human cells, including tumor cells, before the discovery can transition to possible medical applications. The group is also investigating the possibility that cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, might influence the action of SDC4 and alter the behavior of cells resistant to anoikis. The researcher added that 'the discovery of SDC4's role in metastasis opens the door for a range of new studies. One of our lines of inquiry is to test whether cannabidiol can reverse the malignant behavior of anoikis-resistant cells by modulating SDC4 expression or interfering with signaling pathways that support unregulated growth. This would be an interesting approach, but we are still in the early stages of the research.'
The work received support from FAPESP, CNPq, Capes, and Finep, and the results were published in the journal Cytotechnology. This discovery helps reveal new mechanisms that tumors use to advance and supports the search for more precise strategies to fight cancer.
