Overexpressed human CD44s promotes lung colonization during micrometastasis of murine fibrosarcoma cells: facilitated retention in the lung vasculature.

Overexpressed human CD44s promotes lung colonization during micrometastasis of murine fibrosarcoma cells: facilitated retention in the lung vasculature.
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过度表达的人 CD44 在小鼠纤维肉瘤细胞微转移过程中促进肺部定植:促进肺血管系统中的滞留。

DOI:
10.1073/pnas.94.24.13233
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发表时间:
1997
影响因子:
11.1
通讯作者:
Culp,LA
Culp,LA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kogerman,P;Sy,MS;Culp,LA

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正常非转移性鼠白血病转化的BALB/c 3 T3细胞,转染人CD 44 s基因(hCD 44 s),获得自发转移到肺的能力。在实验转移模型中分析了这种促进微转移的机制。人CD 44 s过表达促进了早期阶段的几倍(最初的植入和随后的稳定的肿瘤细胞),但不相关的后期阶段(随后的生长)的肺实验性微转移。通过注射亲代(非转移性)和CD 44 s转染细胞的混合群体,显示肿瘤和亲代细胞之间的细胞-细胞粘附不受hCD 44 s促进,但促进细胞-细胞粘附至肺内皮或特别是转染细胞之间(通过透明质酸)可能是机制。用hCD 44 ε阴性原发性肿瘤细胞和肺微转移细胞的hCD 44 ε阳性或阴性变体获得的结果(s.c.注射转染子)证实了CD 44 s过表达对于实验性肺转移的早期而非晚期的重要性。因此,CD 44 s是一种转移促进分子,与原发性肿瘤生长无关,但在最早期促进肺微转移。
Normally nonmetastatic murinesis-transformed BALB/c 3T3 cells, transfected with human CD44s gene (hCD44s), acquire spontaneous metastatic capacity to the lung. The mechanism(s) of this facilitated micrometastasis was analyzed in an experimental metastasis model. Human CD44s overexpression promoted the earliest stages severalfold (initial implantation and subsequent stabilization of tumor cells) but was irrelevant for later stages (subsequent outgrowth) of lung experimental micrometastasis. By injecting mixed populations of parental (nonmetastatic) and CD44s-transfected cells, it was shown that cell–cell adhesion between tumor and parental cells was not promoted by hCD44s but that promotion of cell–cell adhesion to lung endothelium or specifically between transfected cells (via hyaluronan) are likely mechanisms. Results obtained with hCD44s-negative primary tumor cells and hCD44s-positive or -negative variants of lung micrometastatic cells (after s.c. injection of transfectants) confirmed the importance of CD44s overexpression for early but not late stages of experimental lung metastasis. Therefore, CD44s represents a metastasis-facilitating molecule that is irrelevant for primary tumor outgrowth but that promotes micrometastasis to the lungs at the very earliest stages.
通过自分泌生长因子机制(包括 PDGF)上调 c-sis 转化的 balb/c 3T3 细胞中的 CD44。
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发表时间: 1997
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影响因子: 3.4
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发表时间: 1996
影响因子: 5.6
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