MUCIN PRODUCTION BY HUMAN COLONIC-CARCINOMA CELLS CORRELATES WITH THEIR METASTATIC POTENTIAL IN ANIMAL-MODELS OF COLON CANCER METASTASIS
MUCIN PRODUCTION BY HUMAN COLONIC-CARCINOMA CELLS CORRELATES WITH THEIR METASTATIC POTENTIAL IN ANIMAL-MODELS OF COLON CANCER METASTASIS
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DOI：
10.1172/jci115063
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发表时间：
1991-03-01
影响因子：
15.9
通讯作者：
KIM, YS
中科院分区：
文献类型：
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作者：
BRESALIER, RS;NIV, Y;KIM, YS
粘液性结直肠癌患者的特征性表现为晚期疾病，然而，结肠癌细胞产生粘蛋白与其转移潜力之间的关系仍不清楚。因此，我们试图通过采用结肠癌转移的动物模型来确定人结肠癌细胞的粘蛋白产生与转移能力之间的关系。LS LiM 6是一种在裸鼠盲肠生长期间具有高肝转移能力的结肠癌细胞系，与转移性差的亲本细胞系LS 174 T相比，其产生的代谢标记的细胞内粘蛋白多两倍，并向培养基中分泌多四至五倍的粘蛋白。这伴随着通过与人肠粘蛋白cDNA探针的印迹杂交检测到的poly（A）+ RNA的类似升高，选择高粘蛋白合成能力（HM 7）或低粘蛋白合成能力（LM 12）的LS 174 T变体也在盲肠生长后产生转移，并在脾转移后定殖在肝脏。门静脉注射与它们产生粘蛋白的能力成比例。抑制粘蛋白糖基化的芳基糖苷苄基-α-N-乙酰半乳糖胺大大减少肝移植后脾门静脉注射的肿瘤细胞。这些数据表明，人结肠癌细胞产生的粘蛋白与其转移潜力相关，并影响其在实验模型系统中定殖肝脏的能力。
Patients with mucinous colorectal cancers characteristically present with advanced disease, however, the relationship between mucin production by colon cancer cells and their metastatic potential remains unclear. We therefore sought to define the relationship between mucin production by human colon cancer cells and metastatic ability by employing animal models of colon cancer metastasis. LS LiM 6, a colon carcinoma cell line with high liver metastasizing ability during cecal growth in nude mice produced twofold more metabolically labeled intracellular mucin and secreted four- to fivefold more mucin into the culture medium compared to poorly metastatic parental line LS174T. This was accompanied by a similar elevation in poly(A)+ RNA detected by blot hybridization with a human intestinal mucin cDNA probe, and increases in mucin core carbohydrate antigens determined immunohistochemically.Variants of LS174T selected for high (HM 7) or low (LM 12) mucin synthesizing capacity also yielded metastases after cecal growth and colonized the liver after splenic-portal injection in proportion to their ability to produce mucin. Inhibition of mucin glycosylation by the arylglycoside benzyl-alpha-N-acetylgalactosamine greatly reduced liver colonization after splenic-portal injection of the tumor cells. These data suggest that mucin production by human colon cancer cells correlates with their metastatic potential and affects their ability to colonize the liver in experimental model systems.