Mesothelial cells induce the motility of human ovarian carcinoma cells

Rieppi, Monica; Vergani, Veronica; Gatto, Carmen; Zanetta, Gerardo; Allavena, Paola; Taraboletti, Giulia; Giavazzi, Raffaella

doi:10.1002/(sici)1097-0215(19990118)80:2<303::aid-ijc21>3.3.co;2-n

Cited by 18 publications

(28 citation statements)

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“…LP-9) or isolated from malignant ascites. 7,8,10,13 However, it has been determined that there are differences in the expression of mesothelial specific markers depending on the origin of the cells.14 Current studies also do not address the role of fibroblasts in the adhesion and invasion of ovarian cancer cells. In addition, most published studies have only investigated metastasis of ovarian cancer cells to the abdominal peritoneum, and inferred from these observations that the mechanisms involved in metastasis to the omentum are similar.…”

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“…9,10 At the level of the peritoneum, the mesothelial cell layer is attached to a basement membrane (BM) predominantly composed of collagen types I and IV, fibronectin and laminin.…”

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confidence: 99%

“…[6][7][8][9] Mesothelial cells secrete soluble fibronectin, which may play a role in invasion of ovarian cancer cell lines. 9,10 At the level of the peritoneum, the mesothelial cell layer is attached to a basement membrane (BM) predominantly composed of collagen types I and IV, fibronectin and laminin. 11 Primary ovarian cancer cells adhere preferentially to type I collagen, a process that can be blocked with an a 2 b 1 -integrin antibody that inhibits the interaction with collagen.…”

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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

Kenny

Krausz

Yamada

et al. 2007

Intl Journal of Cancer

221

267

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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. ' 2007 Wiley-Liss, Inc.Key words: 3-dimensional culture; 3D; tumor-stroma interaction; metastasis; ovarian cancer Ovarian cancer is typically diagnosed at an advanced stage, because most patients develop clinical symptoms late in the course of the disease, after the tumor has metastasized.1 The most common sites of metastasis from the primary ovarian tumor are the abdominal peritoneum and the omentum. Often the pliable, semitransparent omental tissue is transformed into a dense omental ''cake'' that impinges on the stomach and the transverse colon, causing a bowel obstruction. Even after infragastric removal of the omentum, which is regularly performed for ovarian cancer staging or debulking at the time of surgery, recurrent tumor cells home to residual areas of the omentum at the splenic hilum, the stomach and the transverse colon causing the reappearance of significant clinical symptoms.The majority of ovarian cancers are of epithelial origin, arising from the single layer of cells that covers the ovary, which is separated by a basement membrane from the underlying ovarian stroma.2,3 There are features unique to ovarian cancer that might facilitate its intraperitonel (ip) spread. The ovarian epithelium can adopt a mesenchymal phenotype characterized by cells that lack tight junctions, which makes them prone to exfoliation. 4 Once an ovarian epithelial cell undergoes transformation it is free to disseminate throughout the peritoneal cavity, carried b...

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“…9,10 At the level of the peritoneum, the mesothelial cell layer is attached to a basement membrane (BM) predominantly composed of collagen types I and IV, fibronectin and laminin.…”

mentioning

confidence: 99%

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confidence: 99%

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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

Kenny

Krausz

Yamada

et al. 2007

Intl Journal of Cancer

221

267

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“…Therefore, peritoneal carcinomatosis may occur as the peritoneal stroma environment promotes tumor cell attachment to the peritoneal mesothelium (7). This process requires the interactions between extracellular matrix proteins and signals produced by mesothelial cells and the corresponding adhesion molecules from tumor cells (8).…”

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confidence: 99%

βig-h3 supports gastric cancer cell adhesion, migration and proliferation in peritoneal carcinomatosis

Zhang

Jin

et al. 2012

Molecular Medicine Reports

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Abstract. βig-h3 is an extracellular matrix protein and its expression is highly induced by transforming growth factor (TGF-β). It has also been suggested to play an important role in the growth and invasion of colon and pancreatic cancers. In the present study, we demonstrated that βig-h3 is expressed in mesothelial cells, especially in patients with advanced gastric cancer. The positive rate of βig-h3 was significantly higher in cases with a more invasive and advanced serous-type, with visible peritoneal metastasis, and in peritoneal lavage cytological examination (PLC) (+) and peritoneal lavage fluid CEA mRNA(+) subgroups (p<0.05). Our study also showed that the expression of βig-h3 gradually increased with increasing TGF-β1 concentrations in vitro in a time-dependant manner. In addition, βig-h3 also induced human gastric carcinoma cell line (SGC-7901) cell adhesion in a dose-dependent manner and significantly increased cell migration and proliferation. The results suggest that βig-h3 expression in peritoneal mesothelial cells in gastric cancer patients is a marker of the biological behavior of gastric cancer and plays an important role in the process of peritoneal carcinomatosis.

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“…Historically, several 3D models have been developed to investigate ovarian cancer interactions with the microenvironment. Some of the first models studied ovarian cancer-ECM interface [17][18][19][20][21] , ovarian cancer-mesothelial cell communication 13,14,[21][22][23][24] , or both 25 (reviewed by us 26 ). Niedbala et al discovered that ovarian cancer cells display a quicker and firmer adhesion to ECM than to mesothelial cells or to plastic alone 25 .…”

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Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity

Peters

Schryver

Lengyel

et al. 2015

JoVE

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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. Video LinkThe video component of this article can be found at

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Mesothelial cells induce the motility of human ovarian carcinoma cells

Cited by 18 publications

References 18 publications

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

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

βig-h3 supports gastric cancer cell adhesion, migration and proliferation in peritoneal carcinomatosis

Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity

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