Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA.
Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA.
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DOI：
10.1084/jem.177.5.1231
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发表时间：
1993-05-01
期刊：
影响因子：
--
通讯作者：
Miyake M
中科院分区：
文献类型：
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作者：
Ikeyama S;Koyama M;Yamaoko M;Sasada R;Miyake M
先前我们发现，运动相关蛋白（MRP-1）是单克隆抗体（mAb） M31-15识别的抑制细胞运动的抗原，并且MRP-1的序列与CD9一致。本研究构建了在Abelson小鼠白血病病毒启动子序列控制下表达人MRP-1/CD9 cDNA的质粒。将MRP-1/CD9表达质粒导入中国仓鼠卵巢细胞、人肺腺癌细胞系MAC10 （MRP-1阳性）和人骨髓瘤细胞系ARH77 （MRP-1阴性）。从这些转染的细胞中获得的MRP-1/CD9（过）表达克隆显示，根据MRP-1/CD9的表达程度，细胞运动性（渗透和吞噬动力学轨迹测定）受到抑制。MAC10细胞过表达MRP-1/CD9导致细胞运动抑制（最大73%），并显著抑制细胞生长（最大48%）。然而，在抗体浓度为1-5微克/ml时，mAb M31-15对MAC10细胞生长的抑制作用< 17%，抑制细胞运动90%。这些结果表明MRP-1/CD9直接调节细胞运动，也可能影响细胞生长。在小鼠黑色素瘤BL6细胞- balb /c nu/nu小鼠系统中研究MRP-1 CD9表达对转移的影响。所有表达MRP-1/CD9的转化子的转移潜能均低于亲本BL6细胞。
Previously we showed that motility-related protein (MRP-1) is an antigen recognized by monoclonal antibody (mAb) M31-15 inhibiting cell motility and that the sequence of MRP-1 coincides with that of CD9. In the present study, plasmid was constructed in which human MRP-1/CD9 cDNA is expressed under the control of the Abelson murine leukemia virus promoter sequence. The expression plasmid for MRP-1/CD9 was introduced into Chinese hamster ovary cells, human lung adenocarcinoma cell line MAC10 (MRP-1 positive), and human myeloma cell line ARH77 (MRP-1 negative). All of the MRP-1/CD9 (over)expressing clones obtained from these transfected cells showed suppressed cell motility (penetration and phagokinetic track assays) depending on the degree of expression of MRP-1/CD9. Overexpression of MRP-1/CD9 by MAC10 cells resulted in the suppression of cell motility (maximally 73%) associated with considerable inhibition of the cell growth (maximally 48%). However, the inhibition of the growth of MAC10 cells by mAb M31-15 was < 17% at an antibody concentration of 1-5 micrograms/ml, which inhibits cell motility by > 90%. These results suggest that MRP-1/CD9 directly regulates cell motility and may also affect cell growth. Effects on metastasis by the expression of MRP-1 CD9 were investigated with mouse melanoma BL6 cells-BALB/c nu/nu mouse system. Metastatic potential of all transformants expressing MRP-1/CD9 was lower than that of parent BL6 cells.