Download To Determine the CCL2 Effect on the Migration of Neural

To Determine the CCL2 Effect on the Migration of Neural Stem-Like Cells in Glioma
Shadi Milani
Mentor: Yi-Hong Zhou
The objective of this experiment is to do an in vitro Boyden chamber analysis to determine the CCL2
effect on the migration of neural stem like-cell (NSLC) of glioma. CCL2 (also called MCP-1) is
consistently overexpressed in a number of glioma cell lines and in some high grade gliomas in
association with microglia infiltration. CCL2 overexpression by glioma cells has been shown to cause
inflammation-induced angiogenesis and consequently tumor progression. CCL2 has been
demonstrated to attract neural precursor cell (NPC) migration using both in vitro Boyden chamber
analysis and in vivo models. In knock-out mice, CCL2 was shown to be the key factor secreted at sites
of neuroinflammation, in the attraction and migration of NPC. Based on the similarities between
NPC and glioma NSLC, we hypothesize that, in glioma, NSLC may be attracted by CCL2 expressed
by glioma mass cells, leading to infiltration, which could promote both tumor progression and
therapeutic resistance and recurrence led by NSLC. Evidence confirming overexpression of the
CCL2 receptor (CCR2) in GBM supports this hypothesis. We will test this hypothesis by direct
disruption of CCL2 function in glioma cells by overexpression of PAX6. The Zhou lab found that
PAX6 suppresses expression of CCL2 and, therefore, has low levels of CCL2 secretion into
condition medium.