Human lymphoblastoid cells produce extracellular matrix degrading enzymes and induce endothelial cell proliferation, migration, morphogenesis, and angiogenesis

被引:76
作者
Vacca, A
Ribatti, D
Iurlaro, M
Albini, A
Minischetti, M
Bussolino, F
Pellegrino, A
Ria, R
Rusnati, M
Presta, M
Vincenti, V
Persico, MG
Dammacco, F
机构
[1] Policlin Bari, Dept Biomed Sci & Human Oncol, Sect Internal Med & Clin Oncol, I-70124 Bari, Italy
[2] Univ Bari, Inst Human Anat Histol & Embryol, I-70124 Bari, Italy
[3] Ist Nazl Ric Canc, I-16132 Genoa, Italy
[4] Univ Turin, Dept Genet Biol & Med Chem, I-10126 Turin, Italy
[5] Univ Brescia, Dept Biomed Sci & Biotechnol, Unit Gen Pathol & Immunol, I-25123 Brescia, Italy
[6] Int Inst Genet & Biophys, I-80125 Naples, Italy
关键词
human lymphoblastoid cells; matrix-degrading enzymes; endothelial cell; angiogenesis;
D O I
10.1007/s005990050018
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Human lymphoproliferative diseases can be hypothesized to invade locally and to metastatize via mechanisms similar to those developed by a variety of solid tumors, i.e., the secretion of extracellular matrix-degrading enzymes and stimulation of angiogenesis. To assess this hypothesis, Namalwa, Raji, and Daudi cell lines (Burkitt's lymphoma), LIK and SB cell lines (B-cell lymphoblastic leukemia), CEM and Jurkat cell lines (T-cell lymphoblastic leukemia), and U266 cell line (multiple myeloma) were evaluated for their capacity to produce matrix metalloproteinase-2 and -9, and urokinase-type plasminogen activator. These cell lines were also assessed for their ability: (1) to produce the angiogenic basic fibroblast growth factor and vascular endothelial growth factor; (2) to induce an angiogenic phenotype in cultured endothelial cells, represented by cell proliferation, chemotaxis, and morphogenesis; (3) to stimulate angiogenesis in different in vivo experimental models. All cell lines expressed the mRNA for one or both metalloproteinases. Namalwa, Raji, LIK, SB, and U266 cells secreted the active form of both metalloproteinases, while Daudi, GEM, and Jurkat cells produced metalloproteinase-2 but not -9. In contrast, urokinase-type plasminogen activator was secreted only by SB cells. While Raji, LIK, SB, GEM, and Jurkat cells secreted both basic fibroblast growth factor and vascular endothelial growth factor, Daudi and U266 cells produced only the former, and Namalwa cells only the latter. Accordingly, the conditioned medium of all cell lines stimulated cell proliferation and/or chemotaxis in cultured endothelial cells, with the exception of that of Namalwa cells which was ineffective. The conditioned medium of CEM and Jurkat cells induced morphogenesis in cultured endothelial cells gown on a reconstituted basement membrane (Matrigel). Lastly, Namalwa, Raji, LIK, SB, U266, GEM, and Jurkat cells induced angiogenesis and mononuclear cell recruitment in the murine Matrigel sponge model and in a chick embryo chorioallantoic membrane assay. The extent of angiogenesis in both models was strictly correlated with the density of the mononuclear cell infiltrate. The results indicate that human lymphoproliferative disease cells possess both local and remote invasive ability via the secretion of matrix-degrading enzymes and the induction of angiogenesis which is fostered by host inflammatory cells and by an intervening ensemble of angiogenic factors.
引用
收藏
页码:55 / 68
页数:14
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