Cell surface expression and functional significance of adhesion molecules on human myeloma‐derived cell lines

Abstract

Multiple myeloma is characterized by the presence of malignant plasma cells predominantly localized in bone marrow. Our prior studies have suggested that human myeloma derived-cell lines adhere specifically to fibronectin and to bone marrow stromal cells (BMSCs) via beta 1 and beta 2 integrins as well as RGD peptide, and that tumour cell to BMSC contact triggers interleukin-6 (IL-6) secretion from BMSCs. Since IL-6 is a growth factor for myeloma, adhesion may be important in paracrine IL-6 mediated tumour cell growth. We therefore examined phenotypic expression of adhesion molecules on the U266 and IM-9 human myeloma-derived cell lines using the panel of monoclonal antibodies (MoAbs) directed at adhesion molecules submitted to the Vth International Conference on Human Leukocyte Differentiation Antigens. U266 and IM-9 myeloma cell lines express mainly CD29, CD49d, VLA-1, CD18, CD54, ICAM-2 and ICAM-3. In contrast, CD49b, VLA-3, CD49f, CD11b, VCAM-1, selectins and selectin-ligands were not expressed on these cell lines. Specific adherence of IM-9 cells to BMSC line LP101 was demonstrated which could be partially blocked by pre-incubation and culture of tumour cells with anti-beta 1 integrin, anti-beta 2 integrin, anti-CD49d, anti-VLA-5, anti-CD11a, anti-CD44 and anti-CD54 MoAbs. The combination of these MoAbs (anti-CD29, CD18, CD11a, CD49d, VLA-5, CD44, CD54, ICAM-2, ICAM-3 MoAbs) decreased but did not completely abrogate binding of IM-9 to BMSCs. Moreover, increases in IL-6 secretion from BMSCs after adherence of IM-9 cells were also partially blocked by these MoAbs. These findings suggest that multiple adhesion pathways may mediate adherence of myeloma cell lines to BMSCs, localizing tumour cells in the marrow microenvironment and triggering IL-6 secretion by BMSCs which may augment tumour cell growth.

Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse

“…LFAl-ICAM-1 interactions have been found to be responsible for homotypic cell aggregations of human MM in culture (Kawano et British Journal of Cancer (1997) 76(4), [451][452][453][454][455][456][457][458][459][460] al, 1991). Several authors have reported the absence of the CD11b marker on all myeloma cells studied (Uchiyama et al, 1992;Van Riet and Van Camp, 1993;Kim et al, 1994;Pellat-Deceunynk et al, 1995a). Mac-I (CD1lb-CD18) is mainly expressed on monocytes and granulocytes and is involved in the adhesion of these cells to endothelial cells and their localization at sites of inflammation.…”

Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration

“…Many hematopoietic tumor cell lines, as well as freshly isolated hematological tumor cells including MM cells, have been reported to produce and secrete VEGF, 18,19,41,42 consistent with an autocrine VEGF pathway. Our previous studies have demonstrated that IL-6 production by BMSCs is stimulated by the adhesion of MM cells, [43][44][45] and more recent studies show increased VEGF secretion in BMSCs after tumor cell binding. Adhesion of MM cells to BMSCs would therefore enhance the VEGF autocrine loop.…”

The role of tumor necrosis factor α in the pathophysiology of human multiple myeloma: therapeutic applications

“…These reports con®rm the critical role of interactions between MM cells and BMSCs in the BM microenvironment. In our previous studies, we have delineated those adhesion molecules on MM cells (CD49d, VLA-4; CD11a, LFA-1; Muc-1) mediating adherence to extracellular matrix proteins (®bronectin) and to BMSCs (CD54, ICAM-1; CD106, VCAM-1) (Uchiyama et al, 1992(Uchiyama et al, , 1993Kim et al, 1994;Teoh and Anderson, 1997). Moreover, TNFa induces VCAM-1 and ICAM-1 expression in a NF-kB dependent manner in human umbilical vein endothelial (HUVE) cells (Palombella et al, 1998).…”