The Crosstalk between Omental Fat and Tumor Cells in Gastrointestinal Malignancies

Gastrointestinal (GI) malignancies are a common cause of cancer- related mortality. While surgery is the only potential curative treatment the majority of patients are deemed inoperable at presentation, resected tumors usually recur, and most patients die due to distant metastasis. Omental spread is a relatively common and untreatable event, representing advanced disease stage that harbors very poor prognosis. This crucial event has been studied to some extent in ovarian cancer, however there is few experimental data regarding omental metastasis of GI cancers, and the exact molecular mechanisms involved in the process remain obscure. The omentum include an abundant amount of adipocytes and to a lesser extent fibroblasts, endothelial cells, various immune cells, and stem cells; therefore, it is reasonable to assume that the omentum which constitute the immediate microenvironment of the metastatic cancer cell plays an active role in the development and progression of omental metastasis. Our results show that factors secreted by the varied cellular components of the omentum enhance gastric and pancreatic tumor proliferation, invasiveness, and survival. Utilizing liquid chromatography tandem mass spectrometry, we identified several cancer related cytokines secreted into the omental fat conditioned medium (CM). A comprehensive mRNA array of pancreatic cancer cells co-cultured with omental fat CM identified specific omental induced molecular alternations that are associated with cancer progression and metastasis. In addition, we conducted several in vivo experiments using different animal models supporting the premise that omental fat increase tumor growth and aggressiveness. Our results provide novel data defining the role of the omentum in GI cancer omental metastasis. Understanding the mechanisms of omental metastasis may improve patient diagnosis and hopefully enable to explore new potential targets for therapy.