Development and Characterization of a System to Examine the Role ofTrkA in Neuroblastoma Differentiation in Chicken Embryos
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.