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>3.0.co;2-w

Cited by 44 publications

(17 citation statements)

References 25 publications

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“…At this time, there are several elegant models available for in vitro studies. Some incorporate two dimensional cultures employing a monolayer of mesothelial cells or extracellular matrix [29][30][31]. These models are vastly restricted by their simplicity as they lack the host of other cells that the omentum is composed of.…”

Section: Discussionmentioning

confidence: 99%

In vitro metastatic colonization of human ovarian cancer cells to the omentum

Khan

Funk

Thiolloy

et al. 2010

Clin Exp Metastasis

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Despite the potentially crucial contributions of the omentum in the regulation of ovarian cancer metastatic growth, it remains a poorly understood organ. Due to its anatomic location and structural fragility, the omentum presents inherent challenges to mechanism-based in vivo studies. Thus, the availability of an ex vivo omental model would, in part, address some of these difficulties posed. Here we describe a technique for identifying, isolating and maintaining ex vivo cultures of omenta from immune-compromised and -competent mice. Ex vivo culture conditions were developed that maintain tissue viability, architecture, and function for up to 10 days. Further experiments demonstrate that the ex vivo culture conditions allow for the proliferation of ovarian cancer cells in vitro and support a similar pattern of microscopic lesions after either intraperitoneal injection of ovarian cancer cells or co-culture of ovarian cancer cells with the omentum. In agreement with previous studies from our laboratory, histologic evaluation of these specimens found that ovarian cancer cells, as well as other peritoneal cancer cells, preferentially accumulate in, and colonize, omental areas rich in immune cells. We now recognize that these are specific, functional structures referred to as milky spots. In sum, these are foundational studies of a readily accessible model, which is easily manipulated and can be immediately used to study the dynamic process of omental colonization. It is hoped that investigators will use the data herein as a starting point for refinements and modifications which will enable them to tailor the model to the specific needs of the experimental question(s) they wish to pursue.

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Section: Discussionmentioning

confidence: 99%

In vitro metastatic colonization of human ovarian cancer cells to the omentum

Khan

Funk

Thiolloy

et al. 2010

Clin Exp Metastasis

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“…Rieppi et al showed that cell free supernatant from cultured mesothelial cells could induce ovarian cancer cells to migrate [52]. uPA, MMP-2, MMP-9, and MMP-13 have been detected in the ascites fluid from ovarian carcinoma patients [24,35,53].…”

Section: Discussionmentioning

confidence: 99%

Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers

Burleson

Hansen

Skubitz

2005

Clin Exp Metastasis

127

114

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Ovarian carcinoma patients frequently develop malignant ascites containing single and aggregated tumor cells, or spheroids. Spheroids have been shown to be resistant to many therapies, but their contribution to ovarian cancer dissemination remains undetermined. We have previously shown that ascites spheroids adhere to extracellular matrix (ECM) proteins and live human mesothelial cells via beta1 integrin subunits. Here, we assessed the ability of spheroids that were generated from the human ovarian carcinoma cell line NIH:OVCAR5 to disseminate and invade in vitro. Spheroids were seeded on ECM proteins for 24 h. While laminin and type IV collagen stimulated some cell migration, spheroids completely disaggregated on type I collagen substrates. A monoclonal antibody against the beta1 integrin subunit significantly inhibited disaggregation on all proteins tested. To test their invasive ability, spheroids were added to monolayers of live human LP9 mesothelial cells. Within 24 h, the spheroids adhered and disaggregated on top of the monolayers, and within a week had established foci of invasion encompassing a 200-fold larger surface area. Addition of a monoclonal antibody against the beta1 integrin subunit drastically reduced spheroid invasion into the mesothelial cell monolayers. GM 6001, a broad-scale matrix metalloproteinase inhibitor, also significantly blocked spheroid invasion into the mesothelial cell monolayers. Epsilon-amino-N-caproic acid, a serine protease inhibitor, partially inhibited spheroid invasion. Based on their ability to attach to, disaggregate on, and invade into live human mesothelial cell monolayers, spheroids should thus be regarded as potential contributors to the dissemination of ovarian cancer.

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“…Kanemoto et al investigated the adhesion, invasion, and colony formation of OVCAR-3 cells to a number of ECMs and reported that a RGD peptide inhibited adhesion to fibronectin and colony formation 44 . Rieppi et al used conditioned media from mesothelial cells and found that it stimulated OvCa invasion through fibronectin 17 .…”

Section: Current In Vitro Models Of Ovarian Cancermentioning

confidence: 99%