p37 induces tumor invasiveness

p37 induces tumor invasiveness
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DOI:
10.1158/1535-7163.mct-05-0040
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发表时间:
2005-07-01
影响因子:
5.7
通讯作者:
Boehlein, SK
Boehlein, SK
中科院分区:
医学2区
文献类型:
--
作者:
Ketcham, CM;Anai, S;Boehlein, SK

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先前的研究表明,人类癌症与猪鼻支原体编码的 p37 蛋白的单克隆抗体检测之间存在统计学显着相关性。 p37的一个潜在机制是它可能促进侵袭和转移。重组p37在体外以剂量依赖性方式增强了两种前列腺癌和两种黑色素瘤细胞系的侵袭性,但对肿瘤细胞生长没有显着影响。此外,通过将癌细胞与抗p37单克隆抗体预孵育,可以完全逆转因暴露于p37而增加的与细胞表面的结合和增强的癌细胞侵袭潜力。序列比较以及三维分子建模揭示了 p37 和流感血凝素 A 之间的相似区域,流感血凝素 A 是一种唾液酸结合蛋白,在病毒进入中发挥着关键作用。发现 p37 与前列腺癌细胞的结合至少部分依赖于唾液酸,因为神经氨酸酶治疗降低了这种结合。总而言之,这些观察结果表明猪鼻支原体可以感染人类,并可能通过 p37 促进肿瘤侵袭。这些结果进一步表明p37可能是癌症治疗的分子靶点。
Previous studies have shown a statistically significant correlation between human carcinomas and monoclonal antibody detection of a Mycoplasma hyorhinis-encoded protein known as p37. A potential mechanism of p37 is that it might promote invasion and metastasis. Recombinant p37 enhanced the invasiveness of two prostate carcinoma and two melanoma cell lines in a dose-dependent manner in vitro, but did not have a significant effect on tumor cell growth. Furthermore, the increased binding to cell surfaces and the enhanced invasive potential of cancer cells from exposure to p37 could be completely reversed by preincubation of the cancer cells with an anti-p37 monoclonal antibody. Sequence comparisons, followed by three-dimensional molecular modeling, revealed a region of similarity between p37 and influenza hemagglutinin A, a sialic acid-binding protein that plays a critical role in viral entry. Binding of p37 to prostate carcinoma cells was found to be at least partially sialic acid dependent because neuraminidase treatment decreased this binding. Taken together, these observations suggest that M. hyorhinis can infect humans and may facilitate tumor invasiveness via p37. These results further suggest that p37 may be a molecular target for cancer therapy.