Suppression of transformed phenotypes of human fibrosarcoma cells by overexpression of recombinant fibronectin.
Suppression of transformed phenotypes of human fibrosarcoma cells by overexpression of recombinant fibronectin.
复制标题
通过重组纤连蛋白的过度表达来抑制人纤维肉瘤细胞的转化表型。
作者：
Hiroki Akamatsu;Keiko Ichihara;Keiichi Ozono;Wataru Kamiike;Hikaru Matsuda;Kiyotoshi Sekiguchi
纤维连接蛋白（FN）从细胞表面的损失已被证明与细胞的恶性转化密切相关。为了阐明FN基质在恶性表型调节中的作用，我们在HT 1080人纤维肉瘤细胞中过表达编码血浆型FN的全长cDNA。过度表达FN的细胞采用了更扁平的形态，并在体外和体内沉积了适度发达的FN基质，尽管整合素α 5 β 1的表达水平保持不变。FN过表达细胞在基质上表现出降低的细胞运动性，并且当皮下注射时生长不良。变成裸鼠FN的过表达也抑制了肿瘤细胞在软琼脂中增殖的能力，而这种抑制通过在软琼脂中包含含有精氨酸-甘氨酸-天冬氨酸（RGD）的肽和针对FN的中央细胞结合结构域的粘附阻断抗体来逆转。无论是细胞的运动性，也不改变生长潜力的过度表达的截断形式的FN缺乏中央细胞结合域。这些结果综合起来表明，FN在细胞周围基质中的沉积增加本身可以通过与识别RGD的整合素（最有可能是α 5 β 1）相互作用来抑制肿瘤细胞的运动性和生长潜力。
Loss of fibronectin (FN) from the cell surface has been shown to be closely associated with malignant transformation of cells. To elucidate the role of the FN matrix in the modulation of malignant phenotypes, we overexpressed a full-length cDNA encoding plasma-type FN in HT1080 human fibrosarcoma cells. The cells overexpressing FN adopted a more flattened morphology and deposited a moderately developed FN matrix both in vitro and in vivo, although the level of expression of integrin alpha5beta1 remained unchanged. FN-overexpressing cells exhibited a reduced cell motility on the substratum and grew poorly when injected s.c. into nude mice. Overexpression of FN also suppressed the ability of the tumor cells to proliferate in soft agar, whereas the suppression was reversed by inclusion in soft agar of the Arg-Gly-Asp (RGD)-containing peptide and adhesion-blocking antibodies against the central cell-binding domain of FN. Neither cell motility nor growth potential was altered by overexpression of a truncated form of FN lacking the central cell-binding domain. These results, taken together, indicate that increased deposition of FN in the pericellular matrix per se can suppress the motility and growth potential of tumor cells through interaction with RGD-recognizing integrins, most likely alpha5beta1.
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DOI：
10.1242/dev.106.2.375
发表时间：
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期刊：
Development (Cambridge, England)
影响因子：
--
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DOI：
--
发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
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通讯作者：
Symington,BE