INHIBITORY EFFECTS OF ADHESION OLIGOPEPTIDES ON THE INVASION OF SQUAMOUS CARCINOMA-CELLS WITH SPECIAL REFERENCE TO IMPLICATION OF ALPHA-V INTEGRINS

INHIBITORY EFFECTS OF ADHESION OLIGOPEPTIDES ON THE INVASION OF SQUAMOUS CARCINOMA-CELLS WITH SPECIAL REFERENCE TO IMPLICATION OF ALPHA-V INTEGRINS
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DOI:
10.1007/bf01198094
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发表时间:
1995-03-01
影响因子:
3.6
通讯作者:
NAKANISHI, I
NAKANISHI, I
中科院分区:
医学3区
文献类型:
--
作者:
KAWAHARA, E;IMAI, K;NAKANISHI, I

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我们使用三种鳞状细胞癌细胞系(HSC-3,低分化型; OSC-19,高分化型; KB细胞,未分化型)研究了体外侵袭相关的粘附事件。在transwell小室中通过基质胶的体外侵袭测定显示HSC-3细胞是最具侵袭性的,OSC-19细胞是中等侵袭性的,KB细胞是最不具侵袭性的。用合成肽RGD、RGDV、RGDS、RGDT、IKVAV和YIGSR进行体外侵袭抑制实验,结果显示RGDV对三种细胞株的侵袭均有明显的抑制作用。还有其他显著抑制侵袭的肽,包括HSC-3的IKVAV和OSC-19的RGDS和YIGSR。HSC-3细胞和OSC-19细胞粘附于纤连蛋白、层粘连蛋白、玻连蛋白和IV型胶原,KB细胞不粘附于层粘连蛋白,但粘附于纤连蛋白、玻连蛋白和IV型胶原。在附着测定中用RGDV肽预处理细胞比用RGDS预处理更有效地降低了这些细胞与玻连蛋白和纤连蛋白结合的能力。抗α v抗体抑制HSC-3、OSC-19和KB细胞与玻连蛋白的粘附,但抗β 1抗体不抑制粘附。免疫荧光显微镜检查显示所有细胞系抗β 5和抗α v抗体阳性,仅HSC-3细胞抗β 3抗体阳性。α 5 β 1在任何细胞系中均未被明确证实。在本实验中使用的合成寡肽中,RGDV是鳞状细胞癌侵袭的最有效抑制剂,并且表明它影响α v β 3-和/或α v β 5-介导的癌细胞侵袭。
We studied invasion-related adhesion events in vitro using three squamous carcinoma cell lines (HSC-3, poorly differentiated type; OSC-19, well-differentiated type; and KB cells, undifferentiated type). An in vitro invasion assay through matrigel in the transwell chamber revealed that HSC-3 cells were most invasive, OSC-19 cells moderately invasive and KB cells least invasive. Inhibition assay of invasion using synthetic peptides RGD, RGDV, RGDS, RGDT, IKVAV and YIGSR, showed that invasion of the three cell lines was significantly inhibited by RGDV. There were other peptides that inhibited invasion significantly including IKVAV for HSC-3, and RGDS and YIGSR for OSC-19. HSC-3 cells and OSC-19 cells adhered to fibronectin, laminin, vitronectin, and type IV collagen, and KB cells did not adhere to laminin but did to fibronectin, vitronectin and collagen type IV. Pretreatment of cells with RGDV peptide in the attachment assay reduced the ability of these cells to bind to vitronectin and fibronectin more efficiently than pretreatment with RGDS. Anti-alpha v antibodies inhibited adhesion of HSC-3, OSC-19 and KB cells to vitronectin, but anti-beta 1 antibodies did not inhibit adhesion. Immunofluorescent microscopic examinations showed that all cell lines were positive for anti-beta 5 and anti-alpha v antibodies, and only HSC-3 cells were positive for anti-beta 3 antibody. alpha 5 beta 1 was not clearly demonstrated in any of the cell lines. RGDV was the most effective inhibitor of squamous cell carcinoma invasion among the synthetic oligopeptides used in this experiment, and it is suggested that it affects alpha v beta 3- and/or alpha v beta 5-mediated carcinoma cell invasion.