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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Role of two types of angiotensin II receptors in colorectal carcinoma progression
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Role of two types of angiotensin II receptors in colorectal carcinoma progression

机译：两种血管紧张素Ⅱ受体在大肠癌进展中的作用

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摘要

Angiotensin II (Ang-II) is a bioactive peptide associated closely with the progression and metastasis of colorectal cancer (CRC). We examined the expression and role of 2 Ang- II receptor types in 20 cases of CRC. Ang-II type 1 receptor (AT1R) protein was localized to the plasma membrane, whereas Ang-II type 2 receptor (AT2R) protein was localized to the nuclei. AT1R expression showed a direct correlation with tumor stage and liver metastasis, whereas AT2R expression showed an inverse correlation. A knockdown study of the AT1R or AT2R with Ang-II treatment was performed to reveal their individual roles in a mouse rectal cell line CMT93, which expresses both Ang-II receptor types. AT2R knockdown showed that the AT1R was associated with tumor growth, survival, invasion and VEGF-A secretion in CMT93 cells in a dose-dependent manner. In contrast, AT1R knockdown showed that the AT2R was associated with increased VEGF-A secretion at low Ang-II concentrations, whereas high concentrations of Ang-II inhibited tumor growth, survival, invasion and VEGF-A secretion. Thus, the AT1R showed a monophasic protumoral effect, while the AT2R showed a biphasic amphitumoral effect. Our findings suggest that a high angiotensinogen condition in the liver might evoke the antitumoral role of the AT2R in CRC cells.
机译：血管紧张素II（Ang-II）是一种与结肠直肠癌（CRC）的进展和转移密切相关的生物活性肽。我们检查了20例CRC中2种Ang-II受体类型的表达和作用。 Ang-II 1型受体（AT1R）蛋白位于质膜，而Ang-II 2型受体（AT2R）蛋白位于细胞核。 AT1R的表达与肿瘤的分期和肝转移有直接的相关性，而AT2R的表达与肿瘤的分期和肝脏的转移呈负相关。进行了以Ang-II处理的AT1R或AT2R的组合研究，以揭示它们在表达两种Ang-II受体类型的小鼠直肠细胞系CMT93中的单独作用。 AT2R敲低表明AT1R与CMT93细胞中的肿瘤生长，存活，侵袭和VEGF-A分泌呈剂量依赖性。相反，AT1R敲低表明AT2R与低Ang-II浓度下增加的VEGF-A分泌有关，而高浓度Ang-II抑制肿瘤的生长，存活，侵袭和VEGF-A分泌。因此，AT1R显示出单相的两性作用，而AT2R显示出两相的两性作用。我们的发现表明，肝脏中较高的血管紧张素原状况可能唤起AT2R在CRC细胞中的抗肿瘤作用。

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