Localization and chemical synthesis of fibronectin peptides with melanoma adhesion and heparin binding activities.

Localization and chemical synthesis of fibronectin peptides with melanoma adhesion and heparin binding activities.
复制标题

具有黑色素瘤粘附和肝素结合活性的纤连蛋白肽的定位和化学合成。

DOI:
10.1021/bi00404a044
复制
发表时间:
1988
期刊:
影响因子:
2.9
通讯作者:
Furcht,LT
Furcht,LT
中科院分区:
生物学3区
文献类型:
--
作者:
McCarthy,JB;Chelberg,MK;Mickelson,DJ;Furcht,LT

文献摘要

参考文献

被引文献

相似文献

明尼苏达大学实验室医学和病理学系,Minneapolis,Minnesota 55455接收于1987年5月27日;修订的Mandarin pt接收于1987年9月23日摘要:肿瘤细胞与细胞外基质的粘附是肿瘤转移的一个重要因素。最近的结果表明,可以从纤连蛋白的蛋白水解酶纯化黑素瘤细胞的多个粘附促进结构域[McCarthy,J. B.,哈根,S. T.,& Furcht,L. T.(1986)J. Cell Biol.102,179-188]。针对来自A链羧基末端的纤连蛋白的胰蛋白酶/组织蛋白酶33 K肝素结合片段产生单克隆抗体。该区域含有肿瘤细胞粘附促进结构域。确定了该片段的氨基末端序列,以及位于纤连蛋白A链中33 K肝素结合片段羧基末端侧的胰蛋白酶3 IK片段。部分序列数据表明,33 K肝素结合片段中不存在乙酰-甘氨酰-乙酰-丝氨酸(RGDS)或相关的乙酰-谷氨酰-乙酰-缬氨酸(REDV),证实了早期的结果,该结果表明细胞通过不依赖RGDS的机制粘附于该片段。两种单克隆抗体,称为AHB-1和AHB-2,识别来自纤连蛋白A和B链羧基末端的肝素结合片段共有的表位。单克隆抗体AHB-2以浓度依赖性方式抑制黑色素瘤粘附到纤连蛋白的33 K肝素结合片段,而单克隆抗体AHB-1对粘附到该片段没有影响。这两种单克隆抗体都不能抑制与完整纤连蛋白的粘附。然而,单克隆AHB-2增强了次优水平的外源性RGDS对细胞粘附至完整纤连蛋白的抑制作用。AHB-2识别纤连蛋白A链和B链羧基端肝素结合区共同的表位。因此,制备了该区域的合成肽,以进一步定位分子的该部分的细胞粘附促进活性。鉴定了两种以浓度依赖性方式促进黑素瘤细胞粘附的肽。这些肽也结合[3 H]肝素在固相结合试验。这些研究支持这样的概念,即黑色素瘤与完整纤连蛋白的粘附是由于多个不同的粘附促进结构域与黑色素瘤细胞表面上的多个功能离散受体相互作用而发生的。肿瘤细胞的侵袭和转移是一个复杂的过程,涉及许多肿瘤和宿主相关因素。理解肿瘤细胞转移生物学的一个重要途径是开发可用于研究细胞粘附于细胞外基质组分的分子基础的工具。几个实验室的工作表明,粘附到细胞外基质是转移过程的一个组成部分。例如,转移性肿瘤细胞与针对层粘连蛋白的抗体的共注射已显示抑制肺转移性结节的形成(Terranova等人,1982年)。最近,分离的层粘连蛋白的肿瘤细胞粘附促进片段(Barsky等人,1984)或来自纤连蛋白的合成粘附破坏肽(Furcht等,1985; Humphries等人,1986)已经显示,当这些细胞在注射到小鼠中之前在这些试剂的存在下离体孵育时,抑制肿瘤细胞的转移行为。这些和许多其他结果表明,肿瘤细胞粘附的作用,在血浆中的分子,基底膜,或细胞外基质。
Department of Laboratory Medicine and Pathology, The University of Minnesota, Minneapolis, Minnesota 55455 Received May 27, 1987; Revised Manuscript Received September 23, 1987 abstract: Tumor cell adhesion to the extracellular matrix is an important consideration in tumor metastasis. Recent results show that multiple adhesion-promoting domains for melanoma cells can be purified from proteolytic digests of fibronectin [McCarthy, J. B., Hagen, S. T., & Furcht, L. T.(1986) J. Cell Biol. 102, 179-188]. Monoclonal antibodies were generated against a tryptic/catheptic 33K heparin binding fragment of fibronectin derived from the carboxyl terminal of the A chain. This region contains a tumor cell adhesion-promoting domain (s). The amino-terminal sequence was determined for this fragment, as well as a tryptic 3 IK fragment which is located to the carboxyl-terminal side of the 33K heparin binding fragment in A chains of fibronectin. The partial sequence data demonstrate that arginyl-glycyl-aspartyl-serine (RGDS) or the related arginyl-glutamyl-aspartyl-valine (REDV) is not present in the 33K heparin binding fragment, confirming earlier results which demonstrated that cells adhere to this fragment by an RGDS-independent mechanism. Two monoclonal antibodies, termed AHB-1 and AHB-2, recognized epitopes common to heparin binding fragments derived from the carboxyl terminus of both the A and B chains of fibronectin. Monoclonal antibody AHB-2 inhibited melanomaadhesion to the 33K heparin binding fragment of fibronectin in a concentration-dependent manner, whereas monoclonal antibody AHB-1 had no effect on adhesion to this fragment. Neither monoclonal antibody inhibited adhesion to intact fibronectin. However, monoclonal AHB-2 potentiated the inhibitory effect of suboptimal levels of exogenous RGDS on cell adhesion to intact fibronectin. AHB-2 recognized an epitope common to both the A-and B-chain carboxyl-terminal heparin binding region of fibronectin. Thus, synthetic peptides of this region were prepared in order to further localize the cell adhesion-promotingactivity of this portion of the molecule. Two peptides were identified which promoted melanoma cell adhesion in a concentration-dependent manner. These peptides also bound [3H] heparin in a solid phase binding assay. The studies support the concept that melanoma adhesion to intact fibronectin occurs as a result of multiple distinct adhesion-promoting domains, which interact with multiple, functionally discrete receptors on the surface of melanoma cells. e invasion and metastasis of tumor cells is a complex process which involves numerous tumor-and host-related factors. One important approach for understanding the biology of metastasizing tumor cells is to develop tools which can be used to study the molecular basis of cell adhesionto components of the extracellular matrix. Work from several labo-ratories has shown that adhesion to the extracellular matrix is an integral part of the metastatic process. For example, coinjection of metastatic tumorcells with antibodies against laminin has been shown to inhibit the formation of pulmonary metastatic nodules (Terranova et al., 1982). More recently, isolated tumor cell adhesion-promoting fragments of laminin (Barsky et al., 1984) or synthetic adhesion-disrupting peptides from fibronectin (Furcht et al., 1985; Humphries et al., 1986) have been shown to inhibit the metastatic behavior of tumor cells when these cells were incubated ex vivo in the presence of these reagents prior to injection into mice. These and many other results suggest a role for tumor cell adhesion to molecules in plasma, basement membranes, or extracellular …
肺部炎症、血浆渗出和肺泡巨噬细胞分泌氧代谢物之间的关系。
DOI: --
发表时间: 1986
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Gerberick,GF;Jaffe,HA;Willoughby,JB;Willoughby,WF
通讯作者: Willoughby,WF
DOI: 10.1164/arrd.1987.135.6.1300
发表时间: 2015-05
期刊: The American review of respiratory disease
影响因子: --
作者:
J. Brieland;R. Kunkel;J. Fantone
通讯作者: J. Brieland;R. Kunkel;J. Fantone
巯基乙酸引发的小鼠腹腔巨噬细胞的氧化代谢:氧、超氧化物和过氧化氢之间的关系以及单层形成的影响。
DOI: --
发表时间: 1981
影响因子: 4.4
作者:
M. Cohen;J. Ryan;R. Root
通讯作者: R. Root
人单核细胞中蛋白激酶 C 活性的重新分布:与呼吸爆发激活的相关性。
DOI: --
发表时间: 1985
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Myers,MA;McPhail,LC;Snyderman,R
通讯作者: Snyderman,R
免疫复合物对大鼠中性粒细胞和肺泡巨噬细胞的体外和体内刺激。
DOI: --
发表时间: 1983
期刊: The American journal of pathology
影响因子: --
作者:
Ward,PA;Duque,RE;Sulavik,MC;Johnson,KJ
通讯作者: Johnson,KJ