The non-receptor-associated tyrosine kinase Syk is a regulator of metastatic behavior in human melanoma cells

被引:41
作者
Hoeller, C
Thallinger, C
Pratscher, B
Bister, MD
Schicher, N
Loewe, R
Heere-Ress, E
Roka, F
Sexl, V
Pehamberger, H
机构
[1] Med Univ Vienna, Dept Dermatol, A-1090 Vienna, Austria
[2] Med Univ Vienna, Dept Pharmacol & Toxicol, A-1090 Vienna, Austria
关键词
experimental melanoma; neoplasm metastasis; SCID mouse;
D O I
10.1111/j.0022-202X.2005.23685.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:1293 / 1299
页数:7
相关论文
共 18 条
[1]   An evidence-based staging system for cutaneous melanoma [J].
Balch, CM ;
Soong, SJ ;
Atkins, MB ;
Buzaid, AC ;
Cascinelli, N ;
Coit, DG ;
Fleming, ID ;
Gershenwald, JE ;
Houghton, A ;
Kirkwood, JM ;
McMasters, KM ;
Mihm, MF ;
Morton, DL ;
Reintgen, DS ;
Ross, MI ;
Sober, A ;
Thompson, JA ;
Thompson, JF .
CA-A CANCER JOURNAL FOR CLINICIANS, 2004, 54 (03) :131-149
[2]   Functional role for Syk tyrosine kinase in natural killer cell-mediated natural cytotoxicity [J].
Brumbaugh, KM ;
Binstadt, BA ;
Billadeau, DD ;
Schoon, RA ;
Dick, CJ ;
Ten, RM ;
Leibson, PJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (12) :1965-1974
[3]   SYK TYROSINE KINASE REQUIRED FOR MOUSE VIABILITY AND B-CELL DEVELOPMENT [J].
CHENG, AM ;
ROWLEY, B ;
PAO, W ;
HAYDAY, A ;
BOLEN, JB ;
PAWSON, T .
NATURE, 1995, 378 (6554) :303-306
[4]  
Cohen C, 2002, CLIN CANCER RES, V8, P3728
[5]   The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells [J].
Coopman, PJP ;
Do, MTH ;
Barth, M ;
Bowden, ET ;
Hayes, AJ ;
Basyuk, E ;
Blancato, JK ;
Vezza, PR ;
McLeskey, SW ;
Mangeat, PH ;
Mueller, SC .
NATURE, 2000, 406 (6797) :742-747
[6]   Malignant transformation of melanocytes to melanoma by constitutive activation of mitogen-activated protein kinase kinase (MAPKK) signaling [J].
Govindarajan, B ;
Bai, XH ;
Cohen, C ;
Zhong, H ;
Kilroy, S ;
Louis, G ;
Moses, M ;
Arbiser, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (11) :9790-9795
[7]   Remodeling of the microenvironment by aggressive melanoma tumor cells [J].
Hendrix, MJC ;
Seftor, EA ;
Kirschmann, DA ;
Quaranta, V ;
Seftor, REB .
TISSUE REMODELING, 2003, 995 :151-161
[8]   MEDICAL PROGRESS - CUTANEOUS MELANOMA [J].
KOH, HK .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (03) :171-182
[9]   The Fc epsilon RI beta subunit functions as an amplifier of Fc epsilon RI gamma-mediated cell activation signals [J].
Lin, SQ ;
Cicala, C ;
Scharenberg, AM ;
Kinet, JP .
CELL, 1996, 85 (07) :985-995
[10]   Syk, a protein-tyrosine kinase, suppresses the cell motility and nuclear factor κB-mediated secretion of urokinase type plasminogen activator by inhibiting the phosphatidylinositol 3'-kinase activity in breast cancer cells [J].
Mahabeleshwar, GH ;
Kundu, GC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (08) :6209-6221