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人结肠癌细胞系在SCID小鼠体内的肿瘤生长和转移类似于临床转移行为。

Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors.

作者信息

Yasui N, Sakamoto M, Ochiai A, Ino Y, Akimoto S, Orikasa A, Kitajima M, Hirohashi S

机构信息

Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.

出版信息

Invasion Metastasis. 1997;17(5):259-69.

PMID:9876220
Abstract

Ten human colorectal cancer (CRC) cell lines were implanted orthotopically into the ceca and also into the livers, muscles and peritoneal cavities of SCID mice in order to analyze the characteristics regulating metastatic behaviors of CRCs. All the CRC cell lines formed tumors in the muscle and cecum, but they could be classified into two groups: (1) six cell lines with high tumorigenicity in the liver (HTLs) forming differentiated tumors, and (2) four with no tumorigenicity in the liver (NTLs) forming poorly differentiated tumors in SCID mice. After orthotopic implantation, NTLs never metastasized to the liver, whereas HTLs did. Therefore, intrahepatic tumorigenicity and differential status were closely associated with liver metastasis whereas differentiation was not associated with lung metastasis. The 6 HTLs demonstrated an inverse correlation between liver metastases and peritoneal dissemination, and immunohistochemistry indicated expression of sLeX, CA19-9 and carcinoembryonic antigen in tumors which correlated well with the liver metastatic rate. We found a strong correlation between liver metastasis and intrahepatic tumorigenicity and could reproduce the clinical correlations between the pattern of the metastatic spread and the differentiation phenotype of CRC in vivo. We consider further examination using this model will be useful for analyzing the complex mechanisms involved in clinically metastasizing CRCs.

摘要

将10种人结肠直肠癌(CRC)细胞系原位植入SCID小鼠的盲肠以及肝脏、肌肉和腹腔,以分析调节CRC转移行为的特征。所有CRC细胞系均在肌肉和盲肠中形成肿瘤,但可分为两组:(1)6种在肝脏中具有高致瘤性的细胞系(HTLs),形成分化良好的肿瘤;(2)4种在肝脏中无致瘤性的细胞系(NTLs),在SCID小鼠中形成低分化肿瘤。原位植入后,NTLs从未转移至肝脏,而HTLs则会转移。因此,肝内致瘤性和分化状态与肝转移密切相关,而分化与肺转移无关。6种HTLs显示肝转移与腹膜播散呈负相关,免疫组织化学表明肿瘤中sLeX、CA19-9和癌胚抗原的表达与肝转移率密切相关。我们发现肝转移与肝内致瘤性之间存在强烈相关性,并且能够在体内重现CRC转移扩散模式与分化表型之间的临床相关性。我们认为使用该模型进行进一步研究将有助于分析临床转移性CRC所涉及的复杂机制。

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