Late stage inhibition of hematogenous melanoma metastasis by cystatin C over-expression.

Late stage inhibition of hematogenous melanoma metastasis by cystatin C over-expression.
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DOI:
10.1186/1475-2867-5-14
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发表时间:
2005-05-17
影响因子:
5.8
通讯作者:
Cox JL
Cox JL
中科院分区:
医学2区
文献类型:
--
作者:
Ervin H;Cox JL

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肿瘤转移是癌症患者治疗失败的常见原因。转移性癌细胞的一个关键特征是它们的侵袭能力。半胱氨酸蛋白酶有助于许多癌细胞类型的侵袭特性。为了分析半胱氨酸蛋白酶对转移的贡献,我们在B16黑色素瘤细胞中过表达天然半胱氨酸蛋白酶抑制剂胱抑素C。我们测量了半胱氨酸蛋白酶抑制剂过表达克隆的体外侵袭与Boyden室型测定。尾静脉注射细胞用于比较肺肿瘤定殖。还分析了原发性肿瘤的皮下肿瘤生长和肿瘤细胞转移。在黑色素瘤细胞注射后的肺组织中测量肿瘤细胞的凋亡。结果表明,胱抑素C过表达的细胞的体外侵袭显着抑制。肺肿瘤定植也减少。增加的肿瘤细胞凋亡被认为是一个重要的因素,可能与该系统中的黑色素瘤转移的肿瘤负荷降低有关。因此,半胱氨酸蛋白酶可能是未来抗转移治疗的靶点。
Tumor metastasis is a frequent cause of treatment failure for cancer patients. A key feature of metastatic cancer cells is their invasive ability. Cysteine proteases contribute to invasive properties of many cancer cell types. To analyze the contribution of cysteine proteases to metastasis we have over-expressed in B16 melanoma cells the natural cysteine protease inhibitor, cystatin C. We measured in vitro invasion of cystatin over-expression clones with Boyden chamber type assays. Tail-vein injections of cells were used to compare lung tumor colonization. Subcutaneous tumor growth and tumor cell metastasis from primary tumors were also analyzed. Apoptosis of tumor cells was measured in lung tissues following melanoma cell injection. Results show the in vitro invasion of cystatin C over-expressing cells was dramatically inhibited. Lung tumor colonization was also reduced. Increased tumor cell apoptosis was found to be an important factor and may be related to the reduced tumor burden noted in this system of melanoma metastasis. Cysteine proteases therefore, may be a target for future anti-metastatic therapies.
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发表时间: 2003-01-01
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影响因子: --
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DOI: 10.1097/00008390-199908000-00005
发表时间: 1999-08-01
期刊: MELANOMA RESEARCH
影响因子: 2.2
作者:
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通讯作者: Darmani, NA