L1CAM-SECRETING CELLS AS PATHFINDERS FOR GLIOBLASTOMA
Date
2018-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Purpose
Glioblastoma multiforme is one of the most common and most malignant forms of brain cancer. Part of what makes this kind of cancer so dangerous is the tendency for tumors to regrow and kill patients after initial tumor removal. Currently, there is no definitive treatment for such cases, nor is there a consensus on the cause. It is hypothesized that part of the cause is the abnormal presence of L1, a cell adhesion molecule. Previous studies have shown that upregulation of L1 increases motility and proliferation in glioblastoma cells. Here, I further investigated the effect of L1’s presence on cancer motility and proliferation, as well as a possible chemotactic relationship that suggests a leader-follower relationship between sources of high L1 concentration and glioblastoma cells.
Methods
In vitro experiments utilizing time-lapse microscopy were used to quantify the velocity and directionality of migrating cancer cells, utilizing L1-positive and L1-negative variants of the human glioblastoma-derived, immortalized cell lines derived from U-118 MG. In vivo experiments used the same cells, with virally labeled fluorescent markers, injected into the optic tecta of developing chick embryos. The chicks’ brains were allowed to develop until embryonic day 15, when they were dissected, fixed in paraformaldehyde, embedded in agar, and sectioned. The sections of brain were immunostained and imaged using confocal microscopy to qualitatively determine relationships between L1-secreting cells and L1-negative cells.
Results
In vitro time-lapse microscopy experiments showed a significant increase in the velocity of migrating glioblastoma cells when sources of L1ecto were present, as well as a significant trend of directional movement toward regions of L1-secreting cells. In vivo chick model experiments showed L1-negative glioblastoma cells appearing to be closely coupled with L1-secreting cells as they moved through the developing brain of a fetal chick.
Conclusions
My results strengthen the argument that the abnormal expression of L1 in glioblastoma multiforme increases the motility and proliferation of glioblastoma cells, and also suggests that sources of L1ecto may guide the directional movement of glioblastoma cells, both in vitro and in vivo. This suggests cells that secrete soluble L1 may act as pathfinders for surrounding cancer cells. Potentially, these L1-positive cells could act as beacons for surrounding cancer cells to regroup around them to form new tumor masses after surgical resection. These findings emphasize the importance of researching molecular inhibitors of L1 as potential adjuvant therapies for brain cancer.
Description
Keywords
Biological Sciences, L1Cam secreting cells, glioblastoma