Activating the GP130 protein slows prostate cancer growth and enhances immune response, offering a potential treatment for aggressive cases.
An international research team, led by Umeå University in Sweden, has demonstrated that a special protein could be pivotal in combating certain types of prostate cancer. Traditionally, treatments have focused on blocking this protein, which is integral to a signaling pathway. However, the researchers now reveal that activating the protein and its associated signaling pathway, rather than inhibiting it, can effectively counteract the cancer.
“Our results show that by activating the signaling pathway, not only does the growth of the tumor be slowed down, but the immune system is then stimulated to actively fight tumor cells,” says Lukas Kenner, visiting professor at the Department of Molecular Biology at Umeå University.
The protein in question is called glycoprotein 130, GP130. It acts as a receptor on the surface of cells. When the GP130 is activated, it sends signals inside the cell via a chain of events, a signaling pathway, that controls how certain genes are expressed.
A special molecule that is activated by this signaling pathway is called STAT3. It is a so-called transcription factor; It acts as a switch that turns genes on or off, and it thus affects how the cell behaves. The STAT3 molecule plays a critical role in the development and spread of tumor cells. Consequently, research has hypothesized that blocking GP130, thereby disrupting the associated signaling pathway, would inhibit STAT3 activity and, in turn, suppress cancer growth.
A Paradigm Shift in Cancer Research
Surprisingly, the current study shows the exact opposite. The researchers instead activated GP130 and with it the signaling pathway in the prostate of genetically modified mice. They could then see that the result was that the growth of the tumor was clearly slowed down in the mice due to the activation of Stat3. Studies of tissue samples from prostate cancer patients also supported these results. There it was possible to see that those high levels of GP130 positively correlated with better survival.
“In the long term, this opens up the possibility for a promising new treatment option for mainly certain forms of aggressive prostate cancer that are currently difficult to treat,” says Lukas Kenner.
The researchers are now proceeding with more studies to be able to confirm the results. More research is needed before we can test the method in studies on patients. The study has been led by Lukas Kenner, a visiting professor at Umeå University, together with Stefan Rose-John, at the University of Kiel, Germany. The Swedish part of the research group has also been led by Jenny Persson, a professor at the Department of Molecular Biology at Umeå University.
Reference: “Cell-autonomous IL6ST activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment” by Christina Sternberg, Martin Raigel, Tanja Limberger, Karolína Trachtová, Michaela Schlederer, Desiree Lindner, Petra Kodajova, Jiaye Yang, Roman Ziegler, Jessica Kalla, Stefan Stoiber, Saptaswa Dey, Daniela Zwolanek, Heidi A. Neubauer, Monika Oberhuber, Torben Redmer, Václav Hejret, Boris Tichy, Martina Tomberger, Nora S. Harbusch, Jan Pencik, Simone Tangermann, Vojtech Bystry, Jenny L. Persson, Gerda Egger, Sarka Pospisilova, Robert Eferl, Peter Wolf, Felix Sternberg, Sandra Högler, Sabine Lagger, Stefan Rose-John and Lukas Kenner, 31 October 2024, Molecular Cancer.
DOI: 10.1186/s12943-024-02114-8
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