Use of a novel 3D culture model to elucidate the role of mesothelial cells, fibroblasts and extra‐cellular matrices on adhesion and invasion of ovarian cancer cells to the omentum
Open Access
- 1 June 2007
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 121 (7), 1463-1472
- https://doi.org/10.1002/ijc.22874
Abstract
The omentum is a major site of ovarian cancer metastasis. Our goal was to establish a three‐dimensional (3D) model of the key components of the omental microenvironment (mesothelial cells, fibroblasts and extracellular matrices) to study ovarian cancer cell adhesion and invasion. The 3D model comprised of primary human fibroblasts extracted from normal human omentum, mixed with ECM and covered by a layer of primary human mesothelial cells, also from normal human omentum. After addition of ovarian cancer cells, the histological appearance of the 3D culture mimicked microscopic metastases to the omentum from patients with ovarian cancer. When ovarian cancer cells, SKOV3ip.1 and HeyA8, were applied to the 3D omental culture, 60% and 68% of all cells attached, respectively, but only 18% and 25% were able to invade. Ovarian cancer cells preferentially adhered to and invaded collagen I, followed by binding to collagen IV, fibronectin, vitronectin, laminin 10 and 1. Omental mesothelial cells significantly inhibited ovarian cancer cell adhesion and invasion, while omental fibroblasts induced adhesion and invasion. This effect is clearly mediated by direct cell–cell contact, since conditioned medium from mesothelial cells or fibroblasts has a minimal, or no, effect on ovarian cancer cell adhesion and invasion. In summary, we have established a 3D model to study the early steps of ovarian cancer metastasis to the human omentum, and found that omental mesothelial cells inhibit, while omental fibroblasts and the ECM enhance, the attachment and invasion of ovarian cancer cells.This publication has 39 references indexed in Scilit:
- Sampling the omentum in ovarian neoplasia: when one block is enoughInternational Journal of Gynecologic Cancer, 2006
- Role of Integrin Receptors for Fibronectin, Collagen and Laminin in the Regulation of Ovarian Carcinoma Functions in Response to a Matrix MicroenvironmentClinical & Experimental Metastasis, 2005
- Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 SecretionCell, 2005
- Laminin isoforms: biological roles and effects on the intracellular distribution of nuclear proteins in intestinal epithelial cellsExperimental Cell Research, 2005
- Stromal fibroblasts in cancer initiation and progressionNature, 2004
- A novel laminin‐induced lysophosphatidic acid autocrine loop in the migration of ovarian cancer cellsThe FASEB Journal, 2003
- Primary culture and mRNA analysis of human ovarian cellsBiological Procedures Online, 2002
- Tumor Growth and Dissemination After Laparotomy and CO2 Pneumoperitoneum: A Rat Ovarian Cancer ModelPublished by Wolters Kluwer Health ,1998
- Fibroblasts Stimulate Human Ovarian Cancer Cell Invasion and Expression of 72-kDa Gelatinase A (MMP-2)Gynecologic Oncology, 1997
- Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal disseminationInternational Journal of Cancer, 1996