DOWN-REGULATION OF E-CADHERIN EXPRESSION IN MADIN DARBY CANINE KIDNEY (MDCK) CELLS INSIDE TUMORS OF NUDE-MICE
DOWN-REGULATION OF E-CADHERIN EXPRESSION IN MADIN DARBY CANINE KIDNEY (MDCK) CELLS INSIDE TUMORS OF NUDE-MICE
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DOI：
10.1002/ijc.2910470623
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发表时间：
1991-04-01
影响因子：
6.4
通讯作者：
VANROY, FM
中科院分区：
文献类型：
--
作者：
MAREEL, MM;BEHRENS, J;VANROY, FM
120 kDa的细胞间粘附分子E-钙粘蛋白定位于上皮连接复合体，参与上皮的组织和维持。 Madin达比犬肾（MDCK）细胞系以稳定的方式表达E-钙粘蛋白，并在体外形成极化的上皮样结构。 哈维鼠肉瘤病毒转化衍生物（MDCK-ras）产生恶性（即，侵袭性和转移性）肿瘤。 我们获得的证据表明，E-钙粘蛋白是下调裸鼠肿瘤，这种下调是可逆的。 从MDCK-ras细胞培养物中体外克隆MDCK-ras-e细胞系。 它们表现为上皮样形态型，并以均匀的高水平表达E-cadherin。 这一特性在体外至少60代中保持不变。 MDCK-ras-e细胞在体外无侵袭性。 然而，当注射到裸鼠体内时，它们产生了侵袭性和转移性肿瘤。 原发肿瘤和大转移瘤是异质性的，显示E-钙粘蛋白阳性的分化良好的上皮结构和E-钙粘蛋白阴性的未分化区域。 在体外早期传代过程中，转移源性细胞培养物含有E-钙粘蛋白阳性和E-钙粘蛋白阴性的MDCK-ras-e细胞。 然而，在进一步的培养过程中，他们恢复了原始MDCK-ras-e细胞系的同质E-cadherin阳性特征。 MDCK-ras-e细胞在体外的行为，与其在体内的行为相比，指出宿主因子的存在，能够下调E-钙粘蛋白的表达。 我们推测这种下调在入侵中起着基本作用。
The 120-kDa cell-cell adhesion molecule E-cadherin is localized at the epithelial junctional complex and participates in the organization and maintenance of epithelia. The Madin Darby canine kidney (MDCK) cell line expresses E-cadherin in a stable way and forms polarized epitheloid structures in vitro. Harvey-murine-sarcoma-virus-transformed derivatives (MDCK-ras) produce malignant (i.e., invasive and metastatic) tumors in nude mice. We obtained evidence that E-cadherin is down-regulated in nude mouse tumors and that this down-regulation is reversible. MDCK-ras-e cell lines were cloned in vitro from MDCK-ras cell cultures. They showed an epithelioid morphotype and expressed E-cadherin at homogeneously high level. This characteristic has been conserved for at least 60 passages in vitro. MDCK-ras-e cells were not invasive in vitro. When injected into nude mice, however, they produced invasive and metastatic tumors. Primary tumors as well as large metastases were heterogeneous, showing E-cadherin-positive well differentiated epithelial structures and E-cadherin-negative undifferentiated areas. Metastasis-derived cell cultures contained both E-cadherin-positive and E-cadherin-negative MDCK-ras-e cells during early passages in vitro. During further culture, however, they regained the homogeneous E-cadherin-positive characteristic of the original MDCK-ras-e cell line. The behavior of MDCK-ras-e cells in vitro, as compared with its in vivo behavior, points to the existence of host factors which are able to down-regulate E-cadherin expression. We hypothesize that this down-regulation plays a basic role in invasion.