The Regression of Glioblastoma Multiforme is Time Dependent in the Wild-type Rat Xenograft Model.

Introduction: Glioblastoma multiforme (GBM) is an aggressive case of primary brain cancer which remains among the most fatal tumors worldwide. Although, some and models have been developed for a better understanding of GBM behavior; a natural model of GBM would improve the efficiency of experimental models of human GBM tumors. We aimed the present study to examine the survival and durability of U87 cells in the brain of wild-type rats.

Methods: U87 cells were intracranially implanted in twenty-one wild-type rats. Tumor size and morphology as well as infiltration of immune cells were investigated at three-time points by H&E and immunohistochemistry (IHC).

Results: The results demonstrated that the inoculation of GBM cells led to the infiltration of host defense system cells which caused immunological regression of the tumor mass after six weeks. While the tumors successfully developed without any sign of host defense invasion in the second week of GBM inoculation. Also, a decrease in tumor size and infiltration of immune system cells were observed in the fourth week.

Conclusion: These data remarkably suggest that time plays a crucial role in activating the immune system against human GBM tumors in rats; it shows that the regression of tumor mass depends on a time slope.

Highlights: A noticeable proliferation of tumor cells was observed in the rat's brain by the second week.The distant metastatic masses of cancer infiltrated into the adjacent normal tissue by the second week.Tumor mass underwent a noticeable diminution in the size by the fourth week.Cancer cells completely regressed by the sixth week due to immunological reactions.In tumor rejection, the effective mechanism depends on immune system activity and the slope of time.

Plain Language Summary: One of the most malignant tumors is the brain tumor in the world. Unfortunately, no effective treatment has yet been found for it. Of course, researchers need efficient animal models to find the appropriate treatment. The xenograft model is one of the tumor models in the laboratory. However, the main challenge is the interaction of the animal's immune system with induced-cancer cells so that the immune system finally rejects the tumor. In this study, we investigated how long the immune system needs to reject induced tumors in the xenograft model completely. For this purpose, we studied the animals in three periods (second week, fourth week, and sixth week). We concluded that the immune system does not recognize the induced cancer cells until the second week of the experiment. It results in the growth of cancer cells and the formation of tumors in the animal brain. However, the immune system begins to recognize the tumor mass after the fourth week which leads to a reduction in metastasis and tumor size. Eventually, the immune system completely rejects the formed tumor in the sixth week.