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Title: L1-CAM knockdown reduces tumorsphere formation in MycN amplified human neuroblastoma stem-like cell lines
Authors: Rashed, Johny
Advisors: Nasr, Zeina 
Subjects: Neuroblastoma
Issue Date: 2016
Childhood neuroblastoma is one of the most malignant types of cancer leading to a high mortality rate. The proto-oncogene Myelocytomatosis Neuroblastoma (MycN) is known to be amplified in this type of cancer, thus promoting high malignancy and resistance. The L1 Cell Adhesion Molecule (L1-CAM) truncation has been found to be upregulated in many types of malignant cancers. Previous studies have concluded that L1-CAM couples with Receptor Tyrosine Kinases (RTKs) that phosphorylate many pathways, leading to gene transcription, mobility, and inhibition of apoptosis. In the current work, we explored the interplay between L1-CAM and MycN as well as the role played by the receptor tyrosine kinases on tumorigenicity in neuroblastoma cells. We investigated the effect of L1-CAM knock-down and RTKs inhibition on tumorsphere formation and cellular proliferation in the MycN-amplified IMR-32 cell line, compared to the non MycN-amplified SK-N-SH neuroblastoma cells. Tumorsphere formation is one of the indicators of aggressiveness in cancer stem-like cells. Cells were grown in stem cell specific medium enriched with growth factors; this growth condition transformed the IMR-32 cell line from a monolayer of adherent cells into large floating tumorspheres that reached 0.5mm in diameter, compared with the SK-N-SH cell line that did not form any. Tumorsphere formation and cellular proliferation was significantly inhibited after L1-CAM knock-down in the IMR-32 cells. Sunitinib malate (Sutent) was used to determine the effect of RTKs inhibition on cell behavior. Sutent treatment (0.2uM) significantly inhibited tumorsphere formation and cellular proliferation in IMR-32 cells. L1-CAM knock down and Sutent did not show any synergy and the si-RNA treatment alone was more efficient than the drug. Taken together, our data shows the importance of L1-CAM interplay with MycN and RTK in MycN amplified neuroblastoma malignancy and motility.
Includes bibliographical references (p.37-44).

Supervised by Dr. Zeina Naser.
Rights: This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder
Ezproxy URL: Link to full text
Type: Thesis
Appears in Collections:UOB Theses and Projects

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