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

Invasion & metastasis Pub Date : 1997-01-01
N Yasui, M Sakamoto, A Ochiai, Y Ino, S Akimoto, A Orikasa, M Kitajima, S Hirohashi
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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.

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人类结直肠癌细胞系在SCID小鼠体内的肿瘤生长和转移与临床转移行为相似。
将10株人结直肠癌(CRC)细胞株原位植入SCID小鼠的盲肠、肝脏、肌肉和腹膜腔,分析其调节CRC转移行为的特性。所有CRC细胞系都在肌肉和盲肠形成肿瘤,但它们可分为两组:(1)6个肝脏高致瘤性细胞系形成分化肿瘤,(2)4个肝脏无致瘤性细胞系在SCID小鼠中形成低分化肿瘤。原位植入后,ntl从未转移到肝脏,而htl则转移到肝脏。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,免疫组化显示肿瘤中sLeX、CA19-9和癌胚抗原的表达与肝转移率呈良好的相关性。我们发现肝转移与肝内致瘤性之间存在很强的相关性,并可以在体内重现转移扩散模式与CRC分化表型之间的临床相关性。我们认为使用该模型的进一步研究将有助于分析临床转移的复杂机制。
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