Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma.
OBJECTIVE
To study the antiangiogenic effect of thalidomide.


METHODS
The expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide.


RESULTS
Thalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM.


CONCLUSIONS
Inhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.
Vacca
Angelo
A
Department of Internal Medicine and Clinical Oncology, Policlinico-Piazza Giulio Cesare, University of Medical School Bari, Italy. a.vacca@dimo.uniba.it
Scavelli
Claudio
C
Montefusco
Vittorio
V
Di Pietro
Giulia
G
Neri
Antonino
A
Mattioli
Michela
M
Bicciato
Silvio
S
Nico
Beatrice
B
Ribatti
Domenico
D
Dammacco
Franco
F
Corradini
Paolo
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010265:Paraproteinemias / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D014471:Umbilical Veins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; D017228:Hepatocyte Growth Factor