METABOLISM OF CARCINOEMBRYONAL ANTIGEN
癌胚抗原的代谢
基本信息
- 批准号:3187250
- 负责人:
- 金额:$ 18.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1986
- 资助国家:美国
- 起止时间:1986-07-01 至 1995-11-30
- 项目状态:已结题
- 来源:
- 关键词:Kupffer's cell athymic mouse binding proteins carcinoembryonal antigen cell adhesion molecules collagenase colorectal neoplasms complement electrofocusing extracellular matrix proteins glycoproteins human tissue laboratory rat liver metabolism metastasis molecular cloning monoclonal antibody neoplasm /cancer immunology nucleic acid sequence protein sequence protein structure function radioimmunoassay radiotracer stromelysin transfection
项目摘要
Carcinoembryonic antigen (CEA) can function as both a homotypic and
heterotypic cell adhesion molecule. Our studies have shown that CEA may
be involved in the development of hepatic metastases from colorectal
cancers possibly as a consequence of its cell adhesion properties. This
study focuses on the structure of CEA binding proteins in the liver. The
major hepatic CEA binding protein is a 80kD subunit Kupffer cell surface
molecule that probably functions as a homodimer. A similar protein is
found on lung alveolar macrophages, but not on peritoneal macrophages or
circulating monocytes. Peptide sequences will be obtained from purified
80kD binding protein and from derived peptides by microsequencing from
PVDF membranes. This data will be used to construct oligonucleotide
probes and as a check on sequences obtained from cloning the gene for the
8OkD binding protein. Both polyclonal and monoclonal antibodies will be
made to the 80kD protein or to derived peptides. The gene responsible
for this protein will be cloned and sequenced from both rat and human
Kupffer cell cDNA libraries by probing expression vectors with synthetic
oligonucleotides, antibodies or using a functional CEA binding assay.
This information will be used to pinpoint functional domains and will be
important in understanding the role of this binding protein in directing
site specific (lung and liver) metastases. The binding site for the 8OkD
protein has been located to the junction of the N-terminal and first loop
domains of CEA. This 10 amino acid sequence contains a pentapeptide with
sequence homology to a pentapeptide (PELPK) found in complement
subcomponent Cls, stromelysin and collagenase 1. Stromelysin and
collagenase are extracellular matrix degrading enzymes that have been
implicated in tumor cell invasion and metastases. The peptide sequence
at the junction of the N-terminal and first loop domain of CEA that binds
to the 8OkD Kupffer cell protein will therefore, be narrowed down to the
minimum structure required for activity. The potential role of the 8OkD
protein as a binding site for stromelysin collagenase and complement Cls
will be investigated. This study expands our knowledge of mechanisms by
which Kupffer cells process glycoproteins and the potential role of the
8OkD binding protein in the mechanism by which colorectal cancer cells
attach and invade in the liver.
癌胚抗原(CEA)可以作为同型和异型抗原发挥作用。
异型细胞粘附分子。 我们的研究表明,CEA可能
参与结直肠癌肝转移的发展
癌症可能是由于其细胞粘附特性。 这
研究的重点是肝脏中CEA结合蛋白的结构。 的
主要的肝CEA结合蛋白是库普弗细胞表面的80 kD亚基
可能作为同二聚体发挥作用的分子。 类似的蛋白质是
在肺泡巨噬细胞上发现,但在腹腔巨噬细胞上未发现,
循环单核细胞 肽序列将从纯化的
80 kD结合蛋白和通过微测序从
聚偏氟乙烯膜。 这些数据将用于构建寡核苷酸
探针,并作为对从克隆该基因获得的序列的检查,
8 OkD结合蛋白。 多克隆抗体和单克隆抗体都将被
对80 kD蛋白质或衍生肽进行修饰。 致病基因
因为这种蛋白质将从大鼠和人类中克隆和测序
通过用合成探针探测表达载体的枯否细胞cDNA文库
寡核苷酸、抗体或使用功能性CEA结合测定。
这些信息将用于查明功能域,并将
重要的是了解这种结合蛋白的作用,
部位特异性(肺和肝)转移。 8 OkD的结合位点
蛋白质已被定位到N-末端和第一环的连接处
CEA领域。 这10个氨基酸序列含有一个五肽,
与补体中发现的五肽(PELPK)的序列同源性
亚组分Cls、溶基质素和胶原酶1。溶基质素和
胶原酶是细胞外基质降解酶,
与肿瘤细胞侵袭和转移有关。 肽序列
在CEA的N-末端和第一环结构域的连接处,
因此,80 kD的库普弗细胞蛋白将被缩小到
活动所需的最低结构。 8 OkD的潜在作用
作为基质溶解素胶原酶和补体Cls的结合位点的蛋白质
将被调查。 这项研究扩展了我们对机制的认识,
库普弗细胞处理糖蛋白的可能作用,
8 OkD结合蛋白在结直肠癌细胞
附着并侵入肝脏。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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PETER THOMAS其他文献
PETER THOMAS的其他文献
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{{ truncateString('PETER THOMAS', 18)}}的其他基金
Characteristics of a putative steroid membrane receptor
假定的类固醇膜受体的特征
- 批准号:
7281260 - 财政年份:2006
- 资助金额:
$ 18.72万 - 项目类别:
Characteristics of a putative steroid membrane receptor
假定的类固醇膜受体的特征
- 批准号:
7882392 - 财政年份:2006
- 资助金额:
$ 18.72万 - 项目类别:
Characteristics of a putative steroid membrane receptor
假定的类固醇膜受体的特征
- 批准号:
7142649 - 财政年份:2006
- 资助金额:
$ 18.72万 - 项目类别:
Characteristics of a putative steroid membrane receptor
假定的类固醇膜受体的特征
- 批准号:
7645014 - 财政年份:2006
- 资助金额:
$ 18.72万 - 项目类别:
Characteristics of a putative steroid membrane receptor
假定的类固醇膜受体的特征
- 批准号:
7448572 - 财政年份:2006
- 资助金额:
$ 18.72万 - 项目类别:
STRUCTURE/FUNCTION OF A HEPATIC CEA BINDING PROTEIN
肝脏 CEA 结合蛋白的结构/功能
- 批准号:
2896051 - 财政年份:1998
- 资助金额:
$ 18.72万 - 项目类别:
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