An orthotopic mouse model of gastric cancer invasion and metastasis.
An orthotopic mouse model of gastric cancer invasion and metastasis.
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DOI：
10.1038/s41598-017-19025-y
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发表时间：
2018-01-16
影响因子：
4.6
通讯作者：
Boussioutas A
中科院分区：
文献类型：
--
作者：
Busuttil RA;Liu DS;Di Costanzo N;Schröder J;Mitchell C;Boussioutas A
胃癌是世界范围内癌症死亡的主要原因，其晚期与肿瘤的侵袭和转移水平有关。目前的研究主要集中在识别和开发针对这些癌症基本特征的有效治疗方法上，然而目前还没有模拟在人类中观察到的侵袭性表型的动物模型。为了解决这个问题，我们开发了一种原位小鼠模型，将胃癌细胞系用荧光素酶标记并注射到胃的浆膜下层。这允许实时监测原发肿瘤的生长和转移，以及通过免疫组织化学定量肿瘤侵袭胃壁的程度。我们根据侵袭和转移的程度建立了三种细胞系特异性模型：AGS细胞在4周内发展为侵袭性肿瘤，无转移迹象；MKN45细胞中度转移，直到第2周侵袭最小；MKN28细胞高度转移，到第1周完全侵袭。这些模型可以作为测试抗肿瘤、抗侵袭和抗转移治疗在胃癌治疗中的疗效的工具，目前胃癌的治疗选择很少。
Gastric cancer is a leading cause of cancer death worldwide, with advanced stage being correlated to the level of tumour invasion and metastasis. Current research is heavily focused on the identification and development of efficacious therapeutics targeting these fundamental hallmarks of cancer, however there are currently no animal models that mimic the invasive phenotypes observed in humans. To address this we have developed an orthotopic mouse model whereby gastric cancer cell lines are tagged with luciferase and injected into the subserosal layer of the stomach. This allows for the monitoring of primary tumour growth and metastasis in real-time as well as quantitation of the degree of tumour invasion through the stomach wall by immunohistochemistry. We have three models based on the degree of invasion and metastasis that are cell line specific: The AGS cells develop into invasive tumours by 4-weeks with no evidence of metastases, MKN45 cells are moderately metastatic with minimal invasion till week 2 and MKN28 cells are highly metastatic and fully invasive by week 1. These models have utility as a tool for testing the efficacy of anti-tumour, anti-invasive and anti-metastatic therapies in the setting of gastric cancer, which currently has poor treatment options.
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影响因子：
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作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
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