Renal cell carcinomas and pancreatic adenocarcinomas produce nidogenin vitro andin vivo

Abstract

The production of nidogen by four renal cell carcinoma (RCC) and three pancreatic adenocarcinoma (PAc) cell lines has been studied in cell culture and in xenografted tumours in nude mice. In RCC cells, immunoreactivity for nidogen was seen only after exposure to monensin to induce cytoplasmic accumulation of secretory proteins. In PAc cells, immunoreaction was also detectable in control cells. Immunoblotting of control and monensin‐exposed cells and immunoprecipitation of culture media of radioactively labelled cells demonstrated the production of nidogen polypeptide of Mr ca. 150000 by six of the seven cell lines. Basement membranes (BMs) and stroma of the xenografted tumours derived from these six cell lines demonstrated immunoreactivity for both human and mouse nidogen, as revealed with species‐specific antibodies. The ability of the cells to produce nidogen in vitro and deposit in vivo was positively correlated with high histological grade of the xenografted tumours, although the small number of cell lines studied calls for further studies to confirm this. The distribution of nidogen in human RCC and PAc specimens was also studied by immunohistochemistry. There was strong immunoreactivity for nidogen in tumour stroma, BM of carcinoma cell nests, and endothelial basal lamina, but no conclusions could be drawn regarding histological grade and immunostaining patterns, because stromal production could not be ruled out. The results show that nidogen is produced by human carcinoma cells both in vitro and in vivo. Copyright © 1999 John Wiley & Sons, Ltd.

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

“…Involved in cell adhesion, migration and growth (Chiquet-Ehrismann and Chiquet, 2003), wound healing, and neovascularization (Hsia and Schwarzbauer, 2005;Trebaul et al, 2007) Ehlers-Danlos syndrome (Burch et al, 1997;Mao and Bristow, 2001) Fibrotic diseases, inflammation, tumorigenesis (Chiquet-Ehrismann and Chiquet, 2003) Thrombospondins (1-5) Involved in cell migration (Yabkowitz et al, 1993), platelet aggregation, inflammatory response, and wound healing (Adams and Lawler, 2004) Thrombospondin-5; pseudoachondroplasia and multiple epiphyseal dysplasia (Posey et al, 2008) Tumor progression (Lawler and Detmar, 2004;Kazerounian et al, 2008); atherosclerosis (Roth et al, 1998;Takahashi et al, 2008) Nidogen/entactin (nidogen 1 and nidogen 2) Involved in cell adhesion (Yi et al, 1998;Grimpe et al, 1999), wound healing (Sephel et al, 1996) and basement membrane stabilization (Ho et al, 2008) Osteoarthritis (Kruegel et al, 2008); cancer and tumor progression (Oivula et al, 1999;Ulazzi et al, 2007;…”

Identification of genes involved in epithelial-mesenchymal transition and tumor progression

“…It is normally synthesized by mesenchymal and myoepithelial cells but not by epithelial cells and is deposited between epithelial cells (Pujuguet et al, 2000). Nidogen has previously been connected to cancer (Oivula et al, 1999) and is found to be highly expressed in renal cell carcinomas (Lohi et al, 1998).…”

Contribution of ADAMTS1 as a tumor suppressor gene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen‐1 and nidogen‐2

“…Nevertheless, very little is known about the potential roles of nidogens during tumor progression. Studies have shown both up‐ and down‐regulation of nidogens in several tumor types although no further analyses were undertaken.…”