Akamatsu H, Ichihara-Tanaka K, Ozono K, Kamiike W, Matsuda H, Sekiguchi K
Research Institute, Osaka Medical Center for Maternal and Child Health, Japan.
Cancer Res. 1996 Oct 1;56(19):4541-6.
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.
细胞表面纤连蛋白（FN）的缺失已被证明与细胞的恶性转化密切相关。为了阐明FN基质在调节恶性表型中的作用，我们在HT1080人纤维肉瘤细胞中过表达了编码血浆型FN的全长cDNA。过表达FN的细胞呈现出更扁平的形态，并且在体外和体内都沉积了适度发育的FN基质，尽管整合素α5β1的表达水平保持不变。过表达FN的细胞在基质上的细胞运动性降低，当皮下注射到裸鼠体内时生长不良。FN的过表达还抑制了肿瘤细胞在软琼脂中增殖的能力，而通过在软琼脂中加入含精氨酸-甘氨酸-天冬氨酸（RGD）的肽和针对FN中央细胞结合域的黏附阻断抗体，这种抑制作用被逆转。缺乏中央细胞结合域的截短形式的FN的过表达既不改变细胞运动性也不改变生长潜力。这些结果综合起来表明，细胞周围基质中FN沉积的增加本身可以通过与识别RGD的整合素（很可能是α5β1）相互作用来抑制肿瘤细胞的运动性和生长潜力。
