However, it has not been clearly demonstrated whether these soluble cell surface PF-04217903 receptors in the plasma are actually originated from the tumor cells. In one study sAXL was detected in the tumor exudates of xenograft mice ; however, the authors used an antibody that detected both murine and human AXL. Hence, the origin of sAXL was not addressed. Furthermore, it has been argued that the increased levels of sAXL seen in the patients did not originate from the tumor cells. The claim was solely based on the lack of correlation between the tumor size and serum levels of AXL in renal cancer patients. In our study the levels of sAXL seem to be correlated with the level of AXL in MPNST cells. In all four MPNST cell lines as well as in the NHSC, the release of sAXL was maintained at constant rate over time in serum free media. As expected, the release of sAXL was the lowest in S462 and NHSC corresponding to the relatively low levels of cellular AXL.. Further, knockdown of AXL reduced the levels of sAXL to the same extend as the reduction of AXL mRNA and protein levels. Furthermore, human sAXL can be detected in the plasma from xenograft mice. Treatment with photodynamic Lipo-ce6 reduced the tumor size and the sAXL levels accordingly. Taken together these findings argue that the sAXL in the plasma originates from the tumor cells, and it might be useful to evaluate sAXL as tumor burden marker in NF1 patients. The role of AXL in the MPNST cells is still unclear. In our study, silencing the expression of AXL did not affect cell proliferation or the subcutaneous tumor growth, but resulted in a slight but significant down regulation of cell migration. In epithelial ovarian cancer, AXL was over-expressed in the advanced metastatic tumors compared to the low grade tumors. The authors noticed reduced tumor growth after intraperitoneal injections of the tumor cells and an adenovirus carrying sAXL was able to reduce the growth of these xenograft tumors. In addition, GAS6-AXL signaling has recently been shown to increase Schwannoma cell matrix adhesion and survival, further arguing for an involvement of AXL in Schwann cell tumorigenesis. Interestingly, the levels of sAXL seem to be more evenly distributed in the female patients compared to the male patients. In the male dermal neurofibroma patients, one patient stood out with 49 ng/ml sAXL compared to the other 16 patients that had between 11.5–20.6 ng/ml. This patient had extreme numbers of neurofibromas, including spinal tumors along all major nerves. Hence, a high sAXL level in this patient supports the general idea of sAXL as tumor burden marker. Within the dermal neurofibroma group, the four male patients with more than 100 dermal neurofibromas, had significant higher sAXL levels than the ten male patients with less than 30 dermal neurofibromas. As a group these high dermal tumor burden patients had comparable levels to the male plexiform patients. In contrast, some of the mild female NF1 patients and even some of the female controls had high levels of sAXL.