A brain tumor is a devastating disease that has destructive growth and causes neuronal cell death. Malignant brain tumors manifest neurodegenerative responses associated with several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.​

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A key objective of my PhD research is to investigate the role of microglia and monocyte-derived macrophages in brain metastases (BrM). In response to the presence of brain tumors, Mg are activated and, together with MDM, can impact the BrM. However, it is still largely unknown to what extent these tumors associated (TA) Mg (TA-Mg) and TA-MDM (collectively termed TAMs) affect BrM
progression, whether they play a similar or different role, do they impact BrM similarly or differently compared to glioma, and how the origin of the metastatic cells and their location in the brain affect the TAMs landscape in the BrM.

 

To address these questions, one needs to distinguish between TA-Mg and TA-MDM effectively. To this end, we employ genetic tracing mouse models that enable us to distinguish between these two cell types. BrM are established in these mouse models by intracardiac or intracranial injection of melanoma cells (B16F10 and RET), Lewis lung carcinoma cells (D122), or breast cancer cells (E0771).

 

In my study, I characterized the spatial interaction of TA-Mg, TA-MDMs, and TA-CP-BAMs with BrMs and their TME and characterized the properties of these cells.

 

Later, I started to investigate the functional role of TA-Mg, TA-MDMs, and TA-CP-BAMs in BrM
development. I have found that BrMs generated by different injection methods (Intracranial and
intracardiac) develop differently.

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Moreover, TA-MG and TA-MDMs distribute differently in different sizes of micrometastasis tumors. This observation can help us understand the mechanism of action of TAMs during different stages of BrM development. And refers to the functionality, I have found that there is a
reduction in Cx3CR1 expression in microglia and MDMs both in melanoma and lung BrM.

 

This study is expected to shed light on the mechanism underlying the regulatory function of microglia-macrophages in BrM, as well as the differences in the function of Mg and macrophages between primary brain tumors (glioma) (our
previous study) and BrM.

 

Our understanding of the mechanisms by which Mg and MDM act in tumor-bearing brains can help us to better understand their role in BrM. In addition, discovering the role of Mg, MDM and BAMs in brain cancers could enhance our understanding of the role of these cells in neurodegenerative diseases and hence the development of new approaches for treating neurodegenerative disorders.​