Soluble AXL: A Possible Circulating Biomarker for Tumor Burden in Neurofibromatosis type 1 (P4.245)

OBJECTIVE: To identify a circulatory biomarker correlated to the tumor burden in neurofibromatosis type 1 (NF1) BACKGROUND: NF1 is the most common tumor predisposition disorder affecting 1/3500 worldwide. Patients are at risk of developing benign (neurofibromas) and malignant peripheral nerve sheath tumors (MPNST). The AXL receptor tyrosine kinase (RTK) has been implicated in several kinds of cancers, but so far no studies have investigated the role of AXL in NF1 related tumorigenesis. Recently, the soluble fraction from the extracellular domain of AXL (sAXL) has been found to be correlated to poor prognosis in patients with renal cancer. DESIGN/METHODS: Firstly, the expression of RTK was evaluated in MPNST cells using protein array. Western blotting was employed to confirm the expression pattern. To evaluate the level of circulatory sAXL, the plasma from NF1 patients with different tumor burden was subjected to ELISA assay. For xenograft mouse model, the MPNST cells with matrigel were injected subcutaneously at the flank of null mice. RESULTS: Compared to normal human Schwann cells, a significantly high expression level of AXL was found in three of the four MPNST cell lines and two of the three primary MPNST tissues. Similarly, the level of sAXL in conditioned media corresponded to the protein and mRNA levels of AXL in the MPNST cell lines. Furthermore, in two different human MPNST xenograft models, the human sAXL could be detected in the mouse plasma. Its level was proportionate to the size of the xenograft tumors, while no human sAXL was detect prior to the formation of the tumors. The level of sAXL was significantly increased in patients with plexiform tumors compared to patients with only dermal neurofibromas, CONCLUSIONS: High expression of RTK, AXL was found in MPNST cells and the sAXL is a novel biomarker correlating to the tumor burden of NF1 patients. Disclosure: Dr. Lee has nothing to disclose. Dr. Johansson has nothing to disclose. Dr. Peng has nothing to disclose. Dr. Huang has nothing to disclose. Dr. Chien has nothing to disclose. Dr. Hua has nothing to disclose. Dr. Kuo has nothing to disclose. Dr. Chen has nothing to disclose.