Kim I, Uchiyama H, Chauhan D, Anderson K C
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115.
Br J Haematol. 1994 Jul;87(3):483-93. doi: 10.1111/j.1365-2141.1994.tb08302.x.
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.
多发性骨髓瘤的特征是存在主要定位于骨髓的恶性浆细胞。我们之前的研究表明，人骨髓瘤衍生细胞系通过β1和β2整合素以及RGD肽特异性黏附于纤连蛋白和骨髓基质细胞（BMSC），并且肿瘤细胞与BMSC的接触会触发BMSC分泌白细胞介素-6（IL-6）。由于IL-6是骨髓瘤的生长因子，黏附在旁分泌IL-6介导的肿瘤细胞生长中可能很重要。因此，我们使用针对提交给第五届国际人类白细胞分化抗原会议的黏附分子的单克隆抗体（MoAb）面板，检测了U266和IM-9人骨髓瘤衍生细胞系上黏附分子的表型表达。U266和IM-9骨髓瘤细胞系主要表达CD29、CD49d、VLA-1、CD18、CD54、ICAM-2和ICAM-3。相反，CD49b、VLA-3、CD49f、CD11b、VCAM-1、选择素和选择素配体在这些细胞系上未表达。已证实IM-9细胞与BMSC系LP101有特异性黏附，用抗β1整合素、抗β2整合素、抗CD49d、抗VLA-5、抗CD11a、抗CD44和抗CD54 MoAb对肿瘤细胞进行预孵育和培养可部分阻断这种黏附。这些MoAb（抗CD29、CD18、CD11a、CD49d、VLA-5、CD44、CD54、ICAM-2、ICAM-3 MoAb）的组合可减少但不能完全消除IM-9与BMSC的结合。此外，这些MoAb也部分阻断了IM-9细胞黏附后BMSC中IL-6分泌的增加。这些发现表明，多种黏附途径可能介导骨髓瘤细胞系与BMSC的黏附，使肿瘤细胞定位于骨髓微环境并触发BMSC分泌IL-6，这可能会促进肿瘤细胞生长。
