Use of a reconstituted basement membrane to study the invasiveness of tumor cells.

Use of a reconstituted basement membrane to study the invasiveness of tumor cells.
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使用重建的基底膜来研究肿瘤细胞的侵袭性。

DOI:
10.1007/978-1-4615-3398-6_14
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发表时间:
1992
影响因子:
--
通讯作者:
Y. Sugioka
Y. Sugioka
中科院分区:
医学4区
文献类型:
--
作者:
Y. Iwamoto;Y. Sugioka

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为了研究肿瘤细胞侵袭的机制,我们使用了基底膜的提取物,这种凝胶基质可以重组为具有生物活性的凝胶基质,主要由IV型胶原、层粘连蛋白、尼多原和硫酸肝素蛋白多糖组成。当层叠在博伊登小室的多孔过滤器上时,这种凝胶形成了正常细胞通过的屏障。当NIH 3T3细胞的条件培养液被用作化学诱导剂以刺激细胞迁移时,恶性细胞能够穿过这一层。因此,在这个系统中研究了各种人类肿瘤细胞,我们发现它们在体外的侵袭性和它们在体内的恶性行为之间有很高的相关性。我们已经使用这种体外侵袭试验来测试可能抑制肿瘤细胞侵袭的因素。IV型胶原酶是由恶性细胞产生的,被认为是侵袭所必需的。事实上,这种酶的抑制剂已经显示出降低了肿瘤细胞的侵袭力。在B1链上有一个5个氨基酸的位置,它被证明可以促进细胞的黏附、迁移和与层粘连蛋白受体的结合,从而抑制肿瘤细胞的侵袭。此外,升高cAMP水平的因子也能够抑制肿瘤细胞的侵袭性。这些数据表明,本文描述的检测系统可以成功地用于研究肿瘤细胞的侵袭活性以及那些可能抑制恶性细胞扩散的因素。
We have used an extract of basement membranes which can be reconstituted into a biologically active gel matrix composed predominantly of collagen IV, laminin, nidogen, and heparin sulfate proteoglycan, in order to study the mechanisms involved in tumor cell invasion. When layered onto a porous filter in a Boyden chamber, the gel forms a barrier to the passage of normal cells. Malignant cells are able to cross this layer when the conditioned medium of NIH 3T3 cells is used as a chemoattractant to stimulate cell migration. A variety of human tumor cells have thus been studied in this system and we find a high correlation between their invasiveness in vitro and their malignant behavior as exhibited in vivo. We have used this in vitro invasion assay to test for factors which might inhibit tumor cell invasion. Collagenase IV is produced by malignant cells and is thought to be required for invasion. Indeed, inhibitors of this enzyme have demonstrated reduced tumor cell invasiveness. One site of five amino acids, on the B1 chain, which has been shown to promote cell adhesion, migration and binding to laminin receptor, was found to inhibit the invasion of tumor cells. In addition, factors which elevated cAMP levels were also able to suppress the invasiveness of tumor cells. These data suggest that the assay system described herein can be successfully utilized to study the invasive activity of tumor cells and those factors that may inhibit the spread of malignant cells.
DOI: 10.1016/s0021-9258(17)43350-3
发表时间: 1984-02
期刊: The Journal of biological chemistry
影响因子: --
作者:
M. Nakajima;T. Irimura;N. Ferrante;G. Nicolson
通讯作者: M. Nakajima;T. Irimura;N. Ferrante;G. Nicolson
DOI: 10.1021/bi00366a050
发表时间: 1986-09-09
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
IRIMURA, T;NAKAJIMA, M;NICOLSON, GL
通讯作者: NICOLSON, GL