Luai Al-Marzouki1,2, Vivian S Stavrakos1,2, Sanjima Pal1, Betty Giannias1, France Bourdeau1, Roni Rayes1, Nicholas Bertos1, Sara Najmeh1,2,3, Jonathan D Spicer1,2,3, Jonathan Cools-Lartigue1,2,3, Swneke D Bailey1,2, Lorenzo Ferri4,5,6, Veena Sangwan7,8. 1. Research Institute of the McGill University Health Centre, Montreal, QC, Canada. 2. Division of Experimental Surgery, Department of Medicine, McGill University, Montreal, QC, Canada. 3. Division of Thoracic and Upper GI Surgery, Montreal General Hospital, 1650 Cedar Avenue, Room L8-325, Montreal, QC, H3G 1A4, Canada. 4. Research Institute of the McGill University Health Centre, Montreal, QC, Canada. lorenzo.ferri@mcgill.ca. 5. Division of Experimental Surgery, Department of Medicine, McGill University, Montreal, QC, Canada. lorenzo.ferri@mcgill.ca. 6. Division of Thoracic and Upper GI Surgery, Montreal General Hospital, 1650 Cedar Avenue, Room L8-325, Montreal, QC, H3G 1A4, Canada. lorenzo.ferri@mcgill.ca. 7. Research Institute of the McGill University Health Centre, Montreal, QC, Canada. veena.sangwan@mcgill.ca. 8. Division of Experimental Surgery, Department of Medicine, McGill University, Montreal, QC, Canada. veena.sangwan@mcgill.ca.
Abstract
BACKGROUND: Adenocarcinoma of the proximal stomach is the fastest rising malignancy in North America. It is commonly associated with peritoneal accumulation of malignant ascites (MA), a fluid containing cancer and inflammatory cells and soluble proteins. Peritoneal metastasis (PM) is the most common site of gastric cancer (GC) progression after curative-intent surgery and is the leading cause of death among GC patients. METHODS/ RESULTS: Using a panel of gastric adenocarcinoma cell lines (human: MKN 45, SNU-5; murine: NCC-S1M), we demonstrate that prior incubation of GC cells with MA results in a significant (> 1.7-fold) increase in the number of cells capable of adhering to human peritoneal mesothelial cells (HPMC) (p < 0.05). We then corroborate these findings using an ex vivo PM model and show that MA also significantly enhances the ability of GC cells to adhere to strips of human peritoneum (p < 0.05). Using a multiplex ELISA, we identify MIF and VEGF as consistently elevated across MA samples from GC patients (p < 0.05). We demonstrate that agents that block the effects of MIF or VEGF abrogate the ability of MA to stimulate the adhesion of GC cells to adhere to human peritoneum and promote both ex vivo and in vivo metastases. CONCLUSION: Agents targeting MIF or VEGF may be relevant to the treatment or prevention of PM in GC patients.
BACKGROUND: Adenocarcinoma of the proximal stomach is the fastest rising malignancy in North America. It is commonly associated with peritoneal accumulation of malignant ascites (MA), a fluid containing cancer and inflammatory cells and soluble proteins. Peritoneal metastasis (PM) is the most common site of gastric cancer (GC) progression after curative-intent surgery and is the leading cause of death among GC patients. METHODS/ RESULTS: Using a panel of gastric adenocarcinoma cell lines (human: MKN 45, SNU-5; murine: NCC-S1M), we demonstrate that prior incubation of GC cells with MA results in a significant (> 1.7-fold) increase in the number of cells capable of adhering to human peritoneal mesothelial cells (HPMC) (p < 0.05). We then corroborate these findings using an ex vivo PM model and show that MA also significantly enhances the ability of GC cells to adhere to strips of human peritoneum (p < 0.05). Using a multiplex ELISA, we identify MIF and VEGF as consistently elevated across MA samples from GC patients (p < 0.05). We demonstrate that agents that block the effects of MIF or VEGF abrogate the ability of MA to stimulate the adhesion of GC cells to adhere to human peritoneum and promote both ex vivo and in vivo metastases. CONCLUSION: Agents targeting MIF or VEGF may be relevant to the treatment or prevention of PM in GC patients.
Authors: Gaya Spolverato; Aslam Ejaz; Yuhree Kim; Malcolm H Squires; George A Poultsides; Ryan C Fields; Carl Schmidt; Sharon M Weber; Konstantinos Votanopoulos; Shishir K Maithel; Timothy M Pawlik Journal: J Am Coll Surg Date: 2014-06-26 Impact factor: 6.113
Authors: Willemieke P M Dijksterhuis; Tiuri E Kroese; Rob H A Verhoeven; Peter S N van Rossum; Stella Mook; Nadia Haj Mohammad; Maarten C C M Hulshof; Suzanne S Gisbertz; Jelle P Ruurda; Martijn G H van Oijen; Richard van Hillegersberg; Hanneke W M van Laarhoven Journal: Eur J Surg Oncol Date: 2022-03-18 Impact factor: 4.037