Growth Regulation of Human Myeloma cells: Regulatory Mechanism in the bone marrow microenvironment.

人骨髓瘤细胞的生长调节：骨髓微环境的调节机制。

基本信息

批准号：
03454525
负责人：
KAWANO Michio
金额：
$ 3.39万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454525/
关键词：
Myeloma Myeloma cells Adhesion molecules Integrin Stromal cells Precursor cells Monoclonal antibody Cell sorter 骨髄ストロ-マ細胞モノクロ-ナル抗体

项目摘要

Since myeloma cells reside in the bone marrow, we investigated the role of microenvironment in the bone marrow on growth of myeloma cells. First, we examined the expression of adhesion molecules on myeloma cells by two-color analysis using anti-CD38 antibody. We found that all myeloma cells located at CD38-strong positive fraction and identified two subpopulations; VLA-5-MPC-1- myeloma cells and VLA-5+MPC-1+ myeloma cells. By a cell sorter,each fraction was isolated and followed by examining the morphology, in vitro proliferative activity and M-protein secretion. These revealed that VLA-5- immature myeloma cells proliferated markedly and responded to interleukin 6(IL-6), while VLA-5+ mature myeloma cells showed low proliferative activities but secreted higher amounts of M-protein in viro significantly. VLA-5+MPC-1+ myeloma cells attached to bone marrow stromal cells tightly, and their interaction was inhibited by the presence of anti-VLA-5 and MPC-1 antibody. Therefore, we could clarify the role of adhesion molecules such as VLA-5 and MPC-1 antigens on growth and differentiation of human myeloma cells: VLA-5-MPC-1- myeloma cells were proliferative immature cells and VLA-5+MPC-1+ mature myeloma cells might be derived from immature myeloma cells and attached to bone marrow stromal cells tightly.

由于骨髓瘤细胞位于骨髓中，因此我们研究了微环境在骨髓中的作用在骨髓细胞生长中。首先，我们使用抗CD38抗体通过两色分析检查了骨髓瘤细胞上粘附分子的表达。我们发现，所有位于CD38-肌阳性分数的骨髓瘤细胞，并鉴定出两个亚群。 VLA-5-MPC-1-骨髓瘤细胞和VLA-5+ MPC-1+骨髓瘤细胞。通过细胞分类器，分离出每个馏分，然后检查形态，体外增殖活性和M蛋白分泌。这些表明VLA-5-未成熟的骨髓瘤细胞显着增殖并对白介素6（IL-6）反应，而VLA-5+成熟的骨髓瘤细胞显示出低增殖活性，但在Viro中分泌了更高量的M蛋白。 VLA-5+ MPC-1+骨髓瘤细胞紧密地附着在骨髓基质细胞上，并且存在抗VLA-5和MPC-1抗体的相互作用受到抑制。因此，我们可以阐明粘附分子（例如VLA-5和MPC-1抗原）对人骨髓瘤细胞的生长和分化的作用：VLA-5-MPC-1-骨髓瘤细胞是增殖性不成熟的细胞，VLA-5+ MPC-1+ MPC-1+成熟的骨髓瘤可能是从不成熟的骨髓瘤和附着的骨骼骨骼蛋白骨骼的细胞而引发的。