Constitutive expression and secretion of proteases in non-metastatic SP1 mammary carcinoma cells and its metastatic sublines.

Constitutive expression and secretion of proteases in non-metastatic SP1 mammary carcinoma cells and its metastatic sublines.
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非转移性 SP1 乳腺癌细胞及其转移性亚系中蛋白酶的组成型表达和分泌。

DOI:
10.1002/ijc.2910480413
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发表时间:
1991
影响因子:
6.4
通讯作者:
Dennis,J
Dennis,J
中科院分区:
医学1区
文献类型:
--
作者:
Korczak,B;Kerbel,RS;Dennis,J

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恶性肿瘤通常以广泛的局部组织侵袭和ECM破坏为特征,这可能是由于分泌蛋白酶的组成表达和活性增加所致。此外,大量不同的蛋白酶活性可能以同时或协调的方式组成性地过表达,从而显著增加细胞的细胞侵袭潜力。为了探索这种关系,我们测量了尿尿酶纤溶酶原激活物(uPA)、组织纤溶酶原激活物(tPA)、转蛋白和组织特异性金属蛋白酶抑制剂(TIMP) mRNA编码的稳态水平;以及非转移性小鼠乳腺癌细胞系SPI分泌的明胶溶酶、酪蛋白溶酶和纤溶酶原激活剂活性,以及由此衍生的4个转移亚系。与亲代SPI肿瘤细胞相比,在转移亚群中,编码金属蛋白酶转蛋白的mRNA增加了15 - 20倍,而TIMP转录物减少了3倍。与SPI细胞相比,转移亚群分泌更高水平的明胶酶(即92 kDa和64 kDa)以及具有溶酪蛋白活性的蛋白酶(即115 kDa和57 kDa)。此外,这些酶被鉴定为中性金属蛋白酶。虽然在SPI和转移亚群中uPA mRNA的量似乎相同,但后者向培养上清中分泌的uPA活性是后者的1.5-3倍。因此,SPI肿瘤模型的转移能力与几种金属蛋白酶活性和uPA分泌增加以及TIMP表达减少有关,这与更具侵袭性的表型一致。
Malignant tumors are generally characterized by extensive local tissue invasion and destruction of ECM which may be due to increased constitutive expression and activity of secreted proteases. Moreover, a large number of diverse protease activities may be constitutively over‐expressed in a simultaneous or co‐ordinated fashion, thereby significantly increasing cellular invasive potential of the cells. To explore this relationship, we have measured steady‐state levels of mRNA coding for uroklnase plasminogen activator (uPA), tissue plasminogen activator (tPA), transin and tissue‐specific inhibitor of metalloproteinases (TIMP); as well as gelatinolytic, caseinolytic and plasminogen activator activities secreted by SPI, a non‐metastatic mouse mammary carcinoma cell line and 4 metastatic sublines derived from it. mRNA encoding metalloproteinase transin was increased 15‐ to 20‐fold, while TIMP transcripts were decreased 3‐fold in the metastatic sublines compared to parental SPI tumor cells. Metastatic sublines secreted higher levels of gelatinase (i.e., 92 kDa and 64 kDa) as well as proteases with caseinolytic activity (i.e., 115 kDa and 57 kDa) when compared with SPI cells. Moreover, these enzymes were identified as neutral metalloproteinases. Although the amount of uPA mRNA appeared to be the same in SPI and the metastatic sublines, the latter secreted 1.5–3 times more uPA activity into the culture supernatants. Metastatic competence in the SPI tumor model is therefore associated with increased secretion of several metalloproteinase activities and uPA, as well as decreased TIMP expression, consistent with a more invasive phenotype.
DOI: 10.1016/0092-8674(86)90613-6
发表时间: 1986-11-21
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发表时间: 1987
影响因子: 11.1
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发表时间: 1977
期刊: The New England journal of medicine
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