title: Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden.
abstract: 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.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Johansson
authors.affiliation: Institute for Systems Biology, Seattle, Washington, United States of America.
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Peng
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Huang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsiung-Fei
authors.initials: HF
authors.lastname: Chien
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.affiliation: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biochemical Science, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.affiliation: Institute for Systems Biology, Seattle, Washington, United States of America.
authors.forename: Chin-Tin
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Genetics National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009442:Neurilemmoma / Q000473:pathology; D018318:Neurofibroma, Plexiform / Q000097:blood*; D009456:Neurofibromatosis 1 / Q000097:blood* / Q000401:mortality / Q000628:therapy; D010766:Phosphorylation; D010778:Photochemotherapy; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood* / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase