INTERACTIONS OF HUMAN OVARIAN TUMOR-CELLS WITH HUMAN MESOTHELIAL CELLS GROWN ON EXTRACELLULAR-MATRIX - AN INVITRO MODEL SYSTEM FOR STUDYING TUMOR-CELL ADHESION AND INVASION
INTERACTIONS OF HUMAN OVARIAN TUMOR-CELLS WITH HUMAN MESOTHELIAL CELLS GROWN ON EXTRACELLULAR-MATRIX - AN INVITRO MODEL SYSTEM FOR STUDYING TUMOR-CELL ADHESION AND INVASION
复制标题
DOI：
10.1016/0014-4827(85)90197-1
复制
发表时间：
1985-01-01
影响因子：
3.7
通讯作者：
BERNACKI, RJ
中科院分区：
文献类型：
--
作者：
NIEDBALA, MJ;CRICKARD, K;BERNACKI, RJ
人类卵巢肿瘤通过直接延伸到腹膜腔中导致肿瘤细胞植入到腹膜表面上而转移。腹膜植入物的成功形成依赖于腹水肿瘤细胞浸润间皮的能力，并与下层细胞外基质（ECM）牢固粘附。为了更详细地研究这一过程，采用在ECM包被的培养皿上生长的人间皮细胞开发了体外模型系统。利用51Cr比率标记的肿瘤细胞定量测定了来自腹水的人卵巢癌细胞附着于ECM、单独ECM或塑料上生长的间皮细胞单层的能力。肿瘤细胞表现出更快速和更坚定的附着ECM比间皮细胞或塑料。使用搅拌来模拟体内腹膜流体动力学和剪切力，发现肿瘤细胞停滞仅限于ECM，但其发生速率比不搅拌时慢。通过相差显微镜评估，肿瘤细胞附着也仅限于受伤间皮中暴露的ECM区域。用扫描电镜和免疫组化染色观察肿瘤细胞诱导的间皮细胞的形态学改变，包括细胞间连接的破坏，导致间皮细胞的退缩，暴露的基础ECM，随后在ECM上的附着和增殖。这个模型系统似乎是有用的阐明卵巢肿瘤细胞的粘附和增殖的机制，并评估各种治疗方式的能力，以阻止肿瘤细胞在腹膜表面的植入，侵袭和生长。
Human ovarian tumors metastasize by direct extension into the peritoneal cavity leading to tumor cell implantation onto peritoneal surfaces. Successful formation of peritoneal implants is dependent on the ability of ascitic tumor cells to infiltrate the mesothelium, and become firmly adherent to the underlying extracellular matrix (ECM). In order to investigate this process in more detail, an in vitro model system was developed employing human mesothelial cells grown on ECM-coated culture dishes. The ability of human ovarian carcinoma cells derived from ascitic fluid to attach to the mesothelial cell monolayer grown on ECM, ECM alone or plastic was quantitated with the use of 51Cr ratio-labelled tumor cells. Tumor cells exhibited a more rapid and firmer attachment to ECM than to the mesothelial cells or to plastic. Using agitation to simulate peritoneal fluid dynamics and shear forces in vivo, tumor cell arrest was found to be limited to the ECM, but it occurred at a slower rate than it did without agitation. Tumor cell attachment was also restricted to areas of exposed ECM in wounded mesothelium as assessed by phase-contrast microscopy. Morphologic alterations of the mesothelium induced by tumor cells were observed with the use of scanning electron microscopy (SEM) and immunohistochemical staining which included disruption of intercellular junctions leading to retraction of mesothelial cells, exposure of underlying ECM, subsequent attachment and proliferation on ECM. This model system would appear to be useful for elucidating mechanisms of ovarian tumor cell adhesion and proliferation, and for assessing various therapeutic modalities for their ability to block tumor cell implantation, invasion and growth on peritoneal surfaces.