Development and Characterization of a System to Examine the Role ofTrkA in Neuroblastoma Differentiation in Chicken Embryos
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Authors
Kuehn, Emily
Issue Date
2010
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Neuroblastoma is one of the most common and fatal pediatric neoplasms, with a
high regression rate in patients. Neuroblastic tumors are derived from neural crest cells
that deviate from proper development and differentiation. Past studies have demonstrated
that behaviors of these tumors and cells are influenced by a variety of extrinsic and
intrinsic cues. Recent work has shown that receptor tyrosine kinases (RTKs) within
neuroblastoma cells have a significant role in their development. Specifically, the Trk
family has been explored to reveal that various Trk protein receptors are co~elated with
favorable (expression of TrkA and/or TrkC) or poor (expression of TrkB) prognosis. The
focus of this study was to determine how migration patterns of neuroblastoma cells are
affected by both the extrinsic cues of the embryonic microenvironment and the intrinsic
cues of Trk expression; and also, to develop an effective method for studying these
effects. Four neuroblastoma lines (LAN6, SK-N-BE(2), SMS-KCN, and SY5Y) were
selected based on their expression of TrkA, and were transplanted into the developing
neural tube of chick embryos. Following transplantation, reincubation, and harvest of
embryos, immunohistochemistry techniques were used to determine final cell fate of each
cell type. All cell types were observed to be multipotent after injection and exhibited
differences in final cell fate. Forced expression of TrkA using AAV plasmids in SK-N-BE(2) cells showed a shift in final cell fate choice, indicating that these receptors play
some role in differentiation and migration patterns of neuroblastoma cells. A major
advancement in this study was the development of effective transplantation and detection
techniques. While the data presented in this study is preliminary, it offers insight into
how TrkA expression may influence the development of neuroblastoma.
Description
v, 42 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.