Vascular endothelial growth factor-C stimulates the migration and proliferation of Kaposi's sarcoma cells

被引:80
作者
Marchiò, S
Primo, L
Pagano, M
Palestro, G
Albini, A
Veikkola, T
Cascone, I
Alitalo, K
Bussolino, F
机构
[1] Univ Turin, Sch Med, Dept Genet Biol & Biochem, Inst Canc Res & Treatment, I-10060 Candiolo, Italy
[2] Univ Turin, Sch Med, Dept Biomed Sci & Oncol, I-10100 Turin, Italy
[3] Natl Inst Canc Res, I-16100 Genoa, Italy
[4] Ctr Adv Biotechnol, I-16100 Genoa, Italy
[5] Univ Helsinki, Haartman Inst, Mol Canc Biol Lab, SF-00014 Helsinki, Finland
关键词
D O I
10.1074/jbc.274.39.27617
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent evidence suggesting vascular endothelial growth factor-C (VEGF-C), which is a regulator of lymphatic and vascular endothelial development, raised the question whether this molecule could be involved in Kaposi's sarcoma (KS), a strongly angiogenic and inflammatory tumor often associated with infection by human immunodeficiency virus-1. This disease is characterized by the presence of a core constituted of three main populations of "spindle" cells, having the features of lymphatic/vascular endothelial cells, macrophagic/ dendritic cells, and of a mixed macrophage endothelial phenotype. In this study we evaluated the biological response of KS cells to VEGF-C, using an immortal cell line derived from a KS lesion (KS IMM), which retains most features of the parental tumor and can induce KS-like sarcomas when injected subcutaneously in nude mice. We show that VEGFR-3, the specific receptor for VEGF-C, is expressed by KS IMM cells grown in vitro and in vivo. In vitro, VEGF-C induces the tyrosine phosphorylation of VEGFR-2, a receptor also for VEGF-A, as well as that of VEGFR-3. The activation of these two receptors in KS IMM cells is followed by a dose-responsive mitogenic and motogenic response. The stimulation of KS IMM cells with a mutant VEGF-C unable to bind and activate VEFGR-2 resulted in no proliferative response and in a weak motogenic stimulation, suggesting that VEGFR-2 is essential in transducing a proliferative signal and cooperates with VEGFR-3 in inducing cell migration. Our data add new insights on the pathogenesis of KS, suggesting that the involvement of endothelial growth factors may not only determine KS-associated angiogenesis, but also play a critical role in controlling KS cell growth and/or migration and invasion.
引用
收藏
页码:27617 / 27622
页数:6
相关论文
共 51 条
[1]   The beta-core fragment of human chorionic gonadotrophin inhibits growth of Kaposi's sarcoma-derived cells and a new immortalized Kaposi's sarcoma cell line [J].
Albini, A ;
Paglieri, I ;
Orengo, G ;
Carlone, S ;
Aluigi, MG ;
DeMarchi, R ;
Matteucci, C ;
Mantovani, A ;
Carozzi, F ;
Donini, S ;
Benelli, R .
AIDS, 1997, 11 (06) :713-721
[2]  
ALLES VV, 1994, BLOOD, V84, P3483
[3]   Chemokines and leukocyte traffic [J].
Baggiolini, M .
NATURE, 1998, 392 (6676) :565-568
[4]   G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator [J].
Bais, C ;
Santomasso, B ;
Coso, O ;
Arvanitakis, L ;
Raaka, EG ;
Gutkind, JS ;
Asch, AS ;
Cesarman, E ;
Gerhengorn, MC ;
Mesri, EA .
NATURE, 1998, 391 (6662) :86-89
[5]  
BECKSTEAD JH, 1985, AM J PATHOL, V119, P294
[6]  
BROOKS JJ, 1986, LANCET, V2, P1309
[7]   PLATELET-ACTIVATING-FACTOR PRODUCED IN-VITRO BY KAPOSIS-SARCOMA CELLS INDUCES AND SUSTAINS IN-VIVO ANGIOGENESIS [J].
BUSSOLINO, F ;
ARESE, M ;
MONTRUCCHIO, G ;
BARRA, L ;
PRINO, L ;
BENELLI, R ;
SANAVIO, F ;
AGLIETTA, M ;
GHIGO, D ;
ROLAPLESZCZYNSKI, M ;
BOSIA, A ;
ALBINI, A ;
CAMUSSI, G .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 96 (02) :940-952
[8]   Molecular mechanisms of blood vessel formation [J].
Bussolino, F ;
Mantovani, A ;
Persico, G .
TRENDS IN BIOCHEMICAL SCIENCES, 1997, 22 (07) :251-256
[9]   Vascular endothelial growth factor C induces angiogenesis in vivo [J].
Cao, YH ;
Linden, P ;
Farnebo, J ;
Cao, RH ;
Eriksson, A ;
Kumar, V ;
Qi, JH ;
Claesson-Welsh, L ;
Alitalo, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (24) :14389-14394
[10]  
Cornali E, 1996, AM J PATHOL, V149, P1851