[Human multiple myeloma cells stimulate differentiation of endothelial cells to form capillary-like networks in two different co-culture systems].

OBJECTIVE

To study the influence of multiple myeloma cells on differentiation of endothelial cells to form capillary-like networks and the role of brain derived neurotrophic factor (BDNF) in this process.

METHODS

Human multiple myeloma cell line RPMI8226 or fresh myeloma cells were co-cultured with human umbilical vein endothelial cells (HUVECs) in two different systems: the contact and the non-contact systems. The HUVECs cultured alone were used as control. The effects of soluble cytokine and adhesion molecule on angiogenesis in HUVECs co-cultured with MM cell were studied by modified Matrigel capillary-like networks formation assay and BDNF levels in co-culture system supernatant by enzyme-linked immunosorbent assay. In the contact co-culture system, the formation of capillary-like networks and the secretion of BDNF were detected again after MM cell was preincubated and cultured with anti-CD29 and anti-CD18 monoclonal antibodies.

RESULTS

In RPMI8226 co-culture system, the number of capillary-like structure was increased in non-contact HUVECs system compared with that in monoculture, but the increase was lower than that of contact HUVECs system (75% vs. 113%). In fresh myeloma cells co-culture system, the numbers of capillary-like structure were 138% and 188% for the non-contact and the contact co-culture systems, respectively, above that in HUVECs cultured alone. The median BDNF concentrations in culture supernatants of mono-cultured, contact co-cultured with RPMI8226, non-contact co-cultured with RPMI8226, contact co-cultured with fresh myeloma cells and non-contact co-cultured with fresh myeloma cells were (12.4 +/- 5.1) ng/ ml, (38.5 +/- 8.2) ng/ml, (31.6 +/- 7.2) ng/ml, (37.1 +/- 8.7) ng/ml and(27.9 +/- 7.6) ng/ml, respectively. Either of the two adhesion molecule monoclonal antibodies reduced the capillary-like networks formation and the BDNF secretion in the contact co-culture system.

CONCLUSION

Human multiple myeloma cells stimulate differentiation of endothelial cells to form capillary-like networks in two different co-culture systems. BDNF takes part in this progress and is modulated by soluble cytokine and adhesion molecule expressed by both kinds of cells.