Investigation of ALCAM's role in glioblastoma senescence

Abstract

Glioblastoma (GBM) is a type of glioma that is the most common brain tumor in the Central Nervous System. Based on this classification, it is the highest-grade astrocytoma (grade IV), highly aggressive and invasive brain cancer. The primary treatment for GBM involves surgical resection to remove as much of the tumor as possible. This is typically followed by radiotherapy and concurrent temozolomide (TMZ) chemotherapy. Despite these multimodal approaches, the prognosis for GBM patients remains poor, with a median survival of approximately 12-16 months. It is already known that the high invasiveness causes the cancer to reach other tissues in the body. If the cells could migrate to other regions but couldn't proliferate, this would increase the lifespan following the diagnosis. Therefore, one of the most important reasons why these treatments are not effective is the fact that cells can escape senescence induced by TMZ. New genetic tools or targets are needed to help to keep the cells in senescence state or to induce senescence more effectively. Here, in this study, we wanted to investigate the role of Activated Cell Adhesion Molecule (ALCAM) in GBM senescence. In the literature, it has been shown that GBM patient survival decreases with the increased ALCAM level. Moreover, in patient-derived xenografts, cells with overexpressed soluble ALCAM showed more aggressiveness. On the contrary, when ALCAM was decreased in GBM cell lines, the colony formation ability increased. Therefore, the role of ALCAM in senescence and especially in GBM senescence, if there is, has remained elusive. To shed light on this unclarified relationship, we used ALCAM targeting small interfering ribonucleic acid (siRNA) and constructed plasmid overexpressing it to manipulate the ALCAM gene level in GBM cells. Expression levels of senescence markers and SA-βgal staining percentage were investigated upon these manipulations. Although significant changes were observed in senescence markers, we cannot say they were consistent or relatable. There is a need for a more comprehensive study to understand the correct relationship. Moreover, conditions like tumor microenvironment, stem cell subpopulation percentage and combinatorial effects should be considered.