Peters Pamela N, Schryver Elizabeth M, Lengyel Ernst, Kenny Hilary
Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, University of Chicago.
Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, University of Chicago;
J Vis Exp. 2015 Dec 31(106):e53541. doi: 10.3791/53541.
The pattern of ovarian cancer metastasis is markedly different from that of most other epithelial tumors, because it rarely spreads hematogenously. Instead, ovarian cancer cells exfoliated from the primary tumor are carried by peritoneal fluid to metastatic sites within the peritoneal cavity. These sites, most notably the abdominal peritoneum and omentum, are organs covered by a mesothelium-lined surface. To investigate the processes of ovarian cancer dissemination, we assembled a complex three-dimensional culture system that reconstructs the lining of the peritoneal cavity in vitro. Primary human fibroblasts and mesothelial cells were isolated from human omentum. The fibroblasts were then mixed with extracellular matrix and covered with a layer of the primary human mesothelial cells to mimic the peritoneal and omental surfaces encountered by metastasizing ovarian cancer cells. The resulting organotypic model is, as shown, used to examine the early steps of ovarian cancer dissemination, including cancer cell adhesion, invasion, and proliferation. This model has been used in a number of studies to investigate the role of the microenvironment (cellular and acellular) in early ovarian cancer dissemination. It has also been successfully adapted to high throughput screening and used to identify and test inhibitors of ovarian cancer metastasis.
卵巢癌的转移模式与大多数其他上皮性肿瘤明显不同，因为它很少通过血行转移。相反，从原发性肿瘤脱落的卵巢癌细胞由腹膜液携带至腹腔内的转移部位。这些部位，最显著的是腹膜和大网膜，是由间皮衬里表面覆盖的器官。为了研究卵巢癌播散的过程，我们构建了一个复杂的三维培养系统，该系统在体外重建了腹膜腔的内衬。从人网膜中分离出原代人成纤维细胞和间皮细胞。然后将成纤维细胞与细胞外基质混合，并用一层原代人 间皮细胞覆盖，以模拟转移的卵巢癌细胞所遇到的腹膜和网膜表面。如图所示，所得的器官型模型用于检查卵巢癌播散的早期步骤，包括癌细胞黏附、侵袭和增殖。该模型已在多项研究中用于研究微环境（细胞和非细胞）在卵巢癌早期播散中的作用。它也已成功应用于高通量筛选，并用于鉴定和测试卵巢癌转移的抑制剂。
