Neurofibromatosis type 1 (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 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 in human plasma, and its level was correlated to poor prognosis in patients with
renal cancer. 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. Treatment with a newly developed
photodynamic therapy, prevented further
tumor growth and resulted in drastically reduced the levels of sAXL compared to that of the control group. Finally, the level of sAXL was significantly increased in patients with plexiform
tumors compared to patients with only dermal
neurofibromas, further supporting the role of sAXL as a marker for NF1 related
tumor burden.