Induction of angiogenesis by normal and malignant plasma cells

被引：103

作者：

Hose, Dirk ^{[1
,2
]}

Moreaux, Jerome ^{[3
,4
]}

Meissner, Tobias ^{[1
]}

Seckinger, Anja ^{[1
]}

Goldschmidt, Hartmut ^{[1
,2
]}

Benner, Axel ^{[5
]}

Mahtouk, Karene ^{[3
,4
]}

Hillengass, Jens ^{[1
,6
]}

Reme, Thierry ^{[3
,4
]}

De Vos, John ^{[3
,4
]}

Hundemer, Michael ^{[1
]}

Condomines, Maud ^{[3
,4
]}

Bertsch, Uta ^{[1
]}

Rossi, Jean-Francois ^{[3
,4
]}

Jauch, Anna ^{[7
]}

Klein, Bernard ^{[3
,4
]}

Moehler, Thomas ^{[1
,2
]}

机构：

[1] Univ Klinikum Heidelberg, Med Klin V, D-69120 Heidelberg, Germany

[2] Natl Ctr Tumorerkrankungen, Heidelberg, Germany

[3] Hop St Eloi, CHU Montpellier, Inst Res Biotherapy, Montpellier, France

[4] INSERM, U847, Montpellier, France

[5] Deutsch Krebsforschungszentrum, Biostat Abt, D-6900 Heidelberg, Germany

[6] Deutsch Krebsforschungszentrum, Abt Radiol, D-6900 Heidelberg, Germany

[7] Univ Klinikum Heidelberg, Inst Humangenet, D-69120 Heidelberg, Germany

来源：

BLOOD | 2009年 / 114卷 / 01期

关键词：

BONE-MARROW ANGIOGENESIS; HEPATOCYTE GROWTH-FACTOR; MULTIPLE-MYELOMA; PROGNOSTIC-FACTOR; STAGING SYSTEM; STEM-CELL; SURVIVAL; EXPRESSION; MODEL; THALIDOMIDE;

D O I：

10.1182/blood-2008-10-184226

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Abundant bone marrow angiogenesis is present in almost all myeloma patients requiring therapy and correlated to treatment response and survival. We assessed the expression of 402 angiogenesis-associated genes by Affymetrix DNA microarrays in 466 samples, including CD138-purified myeloma cells (MMCs) from 300 previously untreated patients, in vivo microcirculation by dynamic contrast-enhanced magnetic resonance imaging, and in vitro angiogenesis (AngioKit-assay). Normal bone marrow plasma cells (BMPCs) express a median of 39 proangiogenic (eg, VEGFA, ADM, IGF-1) and 28 antiangiogenic genes (eg, TIMP1, TIMP2). Supernatants of BMPCs unlike those of memory B cells induce angiogenesis in vitro. MMCs do not show a significantly higher median number of expressed proangiogenic (45) or antiangiogenic (31) genes, but 97% of MMC samples aberrantly express at least one of the angiogenic factors HGF, IL-15, ANG, APRIL, CTGF, or TGFA. Supernatants of MMCs and human myeloma cell lines induce significantly higher in vitro angiogenesis compared with BMPCs. In conclusion, BMPCs express a surplus of proangiogenic over antiangiogenic genes transmitting to the ability to induce in vitro angiogenesis. Aberrant expression of proangiogenic and down-regulation of antiangiogenic genes by MMCs further increases the angiogenic stimulus, together leading to bone marrow angiogenesis at various degrees in all myeloma patients. ( Blood. 2009; 114:128-143)

引用

页码：128 / 143

页数：16

共 54 条

[1] Syndecan-1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival [J].

Andersen, NF ;

Standal, T ;

Nielsen, JL ;

Heickendorff, L ;

Borset, M ;

Sorensen, FB ;

Abildgaard, N .

BRITISH JOURNAL OF HAEMATOLOGY, 2005, 128 (02) :210-217

[2] Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome [J].

Avet-Loiseau, Herve ;

Attal, Michel ;

Moreau, Philippe ;

Charbonnel, Catherine ;

Garban, Frederic ;

Hulin, Cyrille ;

Leyvraz, Serge ;

Michallet, Mauricette ;

Yakoub-Agha, Ibrahim ;

Garderet, Laurent ;

Marit, Gerald ;

Michaux, Lucienne ;

Voillat, Laurent ;

Renaud, Marc ;

Grosbois, Bernard ;

Guillerm, Gaelle ;

Benboubker, Lotfi ;

Monconduit, Mathieu ;

Thieblemont, Catherine ;

Casassus, Philippe ;

Caillot, Denis ;

Stoppa, Anne-Marie ;

Sotto, Jean-Jacques ;

Wetterwald, Marc ;

Dumontet, Charles ;

Fuzibet, Jean-Gabriel ;

Azais, Isabelle ;

Dorvaux, Veronique ;

Zandecki, Marc ;

Bataille, Regis ;

Minvielle, Stephane ;

Harousseau, Jean-Luc ;

Facon, Thierry ;

Mathiot, Claire .

BLOOD, 2007, 109 (08) :3489-3495

[3]

BAIN BJ, 2008, BONE MARROW PATHOLOG, P31

[4] Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies [J].

Barlogie, B ;

Tricot, G ;

Rasmussen, E ;

Anaissie, E ;

van Rhee, F ;

Zangari, M ;

Fassas, A ;

Hollmig, K ;

Pineda-Roman, M ;

Shaughnessy, J ;

Epstein, J ;

Crowley, J .

BLOOD, 2006, 107 (07) :2633-2638

[5] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[6]

Blade Joan, 1998, British Journal of Haematology, V102, P1115, DOI 10.1046/j.1365-2141.1998.00930.x

[7] Hepatocyte growth factor and its receptor c-met in multiple myeloma [J].

Borset, M ;

HjorthHansen, H ;

Seidel, C ;

Sundan, A ;

Waage, A .

BLOOD, 1996, 88 (10) :3998-4004

[8] Delineation of distinct subgroups of multiple myeloma and a model for clonal evolution based on interphase cytogenetics [J].

Cremer, FW ;

Bila, J ;

Buck, I ;

Kartal, M ;

Hose, D ;

Ittrich, C ;

Benner, A ;

Raab, MS ;

Theil, AC ;

Moos, M ;

Goldschmidt, H ;

Bartram, CR ;

Jauch, A .

GENES CHROMOSOMES & CANCER, 2005, 44 (02) :194-203

[9]

DURIE BGM, 1986, SEMIN ONCOL, V13, P300

[10]

DURIE BGM, 1975, CANCER, V36, P842, DOI 10.1002/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO

← 1 2 3 4 5 6 →