According to the research team at Georgia State University, a new protein design can effectively target a cell surface receptor linked to a number of diseases and potential therapeutic treatment for a variety of diseases including cancer. The research findings were reported in the journal of Nature Communications.
In order to understand the new class of protein that could treat cancer, we must ask a vital question, "What is cancer and how can it spread?" Ultimately, cancer is the result of cells that uncontrollably grow, but do not die. The normal cells in our body follow an orderly path of growth, division, and death. Unlike regular body cells, cancer cells do not undergo apoptosis, or programmed cellular death, instead they continue to grow and divide. Unfortunately, this leads to a mass of cancer cells that spreads of out control due to their adhesion (sickness) to the extracellular matrix. The cancer cell will dislodge from the original tumor site and discover a new site where the cells can grow and divide.
ProAgio, which is created from a human protein, targets the cell surface receptor intergrin αVβ₃ at a novel site that has not been targeted by scientists in previous experiments. The researchers found that ProAgio induces apoptosis, or programmed cellular death, of cells that contain intergrin αVβ₃. For several years, the intergrin αVβ₃ has been a primary focus for drug development corporations because the abnormal expression of αVβ₃ is commonly linked to the development of numerous diseases.
What are integrins? Integrins are cell surface receptors that play a critical role with cells attaching to the extracellular matrix. They are biologically composed of different combinations of α (alpha) and β (beta) subunits. Basically, different types of cells contain various pairs of subunits.
"The integrin pair of αVβ₃ is not expressed in high levels of normal tissue," said Zhi-Ren Liu, lead author of the study and professor in the Department of Biology at Georgia State University. "In recent studies, it is associated with a number of different pathological conditions. Therefore, it constitutes a very gapped target for multiple disease treatment."
"We took a unique angle," Lui said. "We designed a protein that binds to a different site. Once the protein binds to the site, it directly triggers cell death. When we're able to kill pathological cells, then we're able to kill the disease."
In this research study, researchers performed extensive cell and molecular testing that confirmed ProAgio interacts and binds well with integrin αVβ₃. Also, they found ProAgio induces apoptosis by recruiting caspase 8, an enzyme that plays an essential role in programmed cell death, to the cytoplasmic area of integrin αVβ₃. ProAgio was very effective in inducing programmed cellular death than other testable agents.
In addition, the researchers conducted tests with mouse models of cancer showed that ProAgio strongly inhibits tumor and blood vessel growth. However, the toxicity tests showed that ProAgio is not toxic to normal body organs and blood vessels.
So, what is the importance behind this research finding? In previous attempts to target the cell surface receptors, scientists were primarily concerned with ligand binding rather than destroying the activation site of cell surface receptors. The cell surface receptor is the main component that contributes to the development and transportation of cancer cells, so this research study discovered groundbreaking developments in cancer research. Hopefully, within the next couple of years, there will be further advancements with the research study that will progress towards human trials.
