[The interaction of vascular endothelial growth factor and interleukin-6 in multiple myeloma].
OBJECTIVE
To study the interaction between human multiple myeloma (MM) cell line and MM-bone marrow stromal cells (BMSCs) modulated by mutual stimulation of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6), and to analyze the role of VEGF and IL-6 in the pathogenesis of MM.


METHODS
MM patient (MM-BMSCs) and normal donor-BMSCs (N-BMSCs) were established from the MNCs of MM and normal bone marrow. ELISA was performed to detect the expression of VEGF and IL-6 in culture supernatants of human MM cell lines U266, MM-BMSCs, N-BMSCs, and co-cultures of U266 and BMSCs in vitro. VEGF and IL-6 were detected in culture supernatants with or without IL-6, anti-IL-6, VEGF, anti-VEGF antibody.


RESULTS
Human MM cell line U266 secreted VEGF, but did not secrete IL-6. BMSCs from MM patients and normal donors secreted both VEGF and IL-6. BMSCs stimulated with recombinant human VEGF induced a time and dose-dependent increase in IL-6 secretion. The effects of VEGF were canceled by monoclonal anti-VEGF antibody. Exogenous IL-6 stimulated VEGF secretion of BMSCs. Importantly, when U266 cell were adhered to BMSCs, there was significant increase of VEGF (2.5 - 5.0 fold, P < 0.05) and IL-6 (5.5 - 9.0 fold, P < 0.05) secretion. The secretion of VEGF or IL-6 in BMSCs alone or co-cultures of BMSCs with U266 were inhibited by anti-human IL-6 or anti-human VEGF antibody. U266 cell stimulated with recombinant human IL-6 induced a dose-dependent increase in VEGF secretion, which was inhibited in the presence of a monoclonal antihuman IL-6 antibody.


CONCLUSIONS
The interaction between myeloma cells and marrow stromal cells modulates the secretion of VEGF and IL-6, facilitates myeloma cells growth and angiogenesis in MM. It plays an important role in the pathogenesis of MM. This study provides a theoretic basis for target therapy in the treatment of bone marrow microenvironment.
Zhang
Lei
L
Department of Hematology, Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing 100020, China. dr_zhlei@sohu.com
Chen
Shi-lun
SL
Chen
Wen-ming
WM
Liu
Jin-wei
JW
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A