Adhesion of Gastric Cancer Cells to the Enteric Nervous System: Comparison between the Intestinal Type and Diffuse Type of Gastric Cancer

胃癌细胞对肠神经系统的粘附:肠型与弥漫型胃癌的比较

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作者:Paul Girot, Nicolas Chapelle, Laetitia Aymeric, Anne Bessard, Alice Prigent, Yann Touchefeu, Christine Varon, Michel Neunlist, Emilie Duchalais, Tamara Matysiak-Budnik

Background

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. The enteric nervous system (ENS) has been suggested to be involved in cancer development and spread.

Conclusion

These results suggest a potential role of enteric neurons in the dissemination of GC cells, especially of the diffuse-type, partly through N-Cadherin.

Methods

Primary culture of gastric ENS (pcgENS), derived from a rat embryo stomach, was developed. The adhesion of GC cells to pcgENS was studied using a co-culture model. The role of N-Cadherin, a cell-adhesion protein, was evaluated.

Objective

To analyze the GC cell adhesion to the ENS in a model of co-culture of gastric ENS with GC cells.

Results

Compared to intestinal-type GC cells, the diffuse-type GC cancer cells showed higher adhesion to pcgENS (55.9% ± 1.075 vs. 38.9% ± 0.6611, respectively, p < 0.001). The number of diffuse-type GC cells adherent to pcgENS was significantly lower in neuron-free pcgENS compared to neuron-containing pcgENS (p = 0.0261 and 0.0329 for AGS and MKN45, respectively). Confocal microscopy showed that GC cells adhere preferentially to the neurons of the pcgENS. N-Cadherin blockage resulted in significantly decreased adhesion of the GC cells to the pcgENS (p < 0.01).

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