BINDING AND DEGRADATION OF HYALURONAN BY HUMAN BREAST-CANCER CELL-LINES EXPRESSING DIFFERENT FORMS OF CD44 - CORRELATION WITH INVASIVE POTENTIAL

BINDING AND DEGRADATION OF HYALURONAN BY HUMAN BREAST-CANCER CELL-LINES EXPRESSING DIFFERENT FORMS OF CD44 - CORRELATION WITH INVASIVE POTENTIAL
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DOI:
10.1002/jcp.1041600209
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发表时间:
1994-08-01
影响因子:
5.6
通讯作者:
UNDERHILL, CB
UNDERHILL, CB
中科院分区:
生物学2区
文献类型:
--
作者:
CULTY, M;SHIZARI, M;UNDERHILL, CB

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在本研究中,我们研究了一组人乳腺癌细胞系的CD 44表达和结合和降解透明质酸的能力。细胞系表达不同量的不同分子量形式的CD 44(85-200 kDa),并且通常,表达最大量的CD 44的那些细胞系是最具侵袭性的,如通过体外测定所判断的。此外,结合和降解透明质酸的能力仅限于表达高水平CD 44的细胞系,这两种功能均被CD 44抗体(爱马仕-1)阻断。此外,[H-3]透明质酸的降解速率与CD 44的量高度相关(r = 0.951,P < 0.0001),以及与细胞的侵袭潜力高度相关。这些细胞的[H-3]透明质酸结合的Scatchard分析显示,它们的结合能力和解离常数存在显著差异。为了确定该偏离的来源,通过凝胶过滤色谱法部分分离了不同分子量形式的CD 44。在所有细胞系中,85 kDa的形式能够结合透明质酸,虽然具有不同的亲和力。相比之下,并非所有高分子量形式的CD 44都具有这种能力。这些结果说明了CD 44分子在侵袭性肿瘤细胞中的多样性,并表明其主要功能之一是降解透明质酸。(C)1994 Wiley-Liss,Inc.
In the present study, we examined a panel of human breast cancer cell lines with regard to their expression of CD44 and ability to bind and degrade hyaluronan. The cell lines expressed varying amounts of different molecular weight forms of CD44 (85-200 kDa) and, in general, those that expressed the greatest amounts of CD44 were the most invasive as judged by in vitro assays. In addition, the ability to bind and degrade hyaluronan was restricted to the cell lines expressing high levels of CD44, and both these functions were blocked by an antibody to CD44 (Hermes-1). Moreover, the rate of [H-3]hyaluronan degradation was highly correlated with the amount of CD44 (r = 0.951, P < 0.0001), as well as with the invasive potential of the cells. Scatchard analysis of the [H-3]hyaluronan binding of these cells revealed the existence of significant differences in both their binding capacity and their dissociation constant. To determine the source of this deviation, the different molecular weight forms of CD44 were partially separated by gel filtration chromatography. In all cell lines, the 85 kDa form was able to bind hyaluronan, although with different affinities. In contrast, not all of the high molecular weight forms of CD44 had this ability. These results illustrate the diversity of CD44 molecules in invasive tumor cells, and suggest that one of their major functions is to degrade hyaluronan. (C) 1994 Wiley-Liss, Inc.