The non-receptor-associated tyrosine kinase Syk is a regulator of metastatic behavior in human melanoma cells.
Melanoma is one of the most aggressive neoplastic transformations and characterized by a high metastatic potential. The current study was performed to assess the impact of "spleen tyrosine kinase" (Syk), a non-receptor-associated tyrosine kinase, on growth and metastatic behavior of melanoma cells in vitro and in a severe combined immunodeficient (SCID)-mouse/human-melanoma xenotransplantation model in vivo. Syk was expressed in melanocytes but was found to be downregulated in melanoma cells. Vector-driven expression of Syk in two different melanoma cell lines did not influence growth speed, but significantly reduced the invasive growth potential of both cell lines in a Matrigel assay in vitro. In a SCID-mouse/human melanoma xenotransplantation model, Syk expressing Mel-Juso cells exhibited delayed and reduced tumor growth. After intravenous as well as subcutaneous injection of tumor cells, Syk-transfected cells formed significantly fewer metastatic tumor lesions than control cells. The presented data define Syk as a novel regulator of metastatic behavior of melanoma cells.
Hoeller
Christoph
C
Department of Dermatology, Medical University, Vienna, Austria. christoph.hoeller@univie.ac.at
Thallinger
Christiane
C
Pratscher
Barbara
B
Bister
Malena D
MD
Schicher
Nikolaus
N
Loewe
Robert
R
Heere-Ress
Elisabeth
E
Roka
Florian
F
Sexl
Veronika
V
Pehamberger
Hubert
H
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D004792:Enzyme Precursors / Q000378:metabolism*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000072377:Syk Kinase; D014183:Transplantation, Heterologous
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse