Role of tumor-stromal interactions in pancreatic cancer invasion and metastases

Pancreatic cancer tumor microenvironment (TME), simply defined as the noncancerous desmoplastic reaction, is considered a key player in all aspects of tumor growth, and progression. The dismal prognosis of pancreatic cancer and disappointing clinical trials has drawn our attention to the TME, particularly to the tumor-stromal interactions. While a myriad of molecular, pathological, and clinical features contribute to the lethality of pancreatic cancer, local invasiveness and distant metastases is a hallmark and leading cause of mortality and morbidity in this ominous cancer. Cancer-associated stromal cells including stellate cells have been implicated in epithelial mesenchymal transition (EMT), a process involved in invasion and metastases. In addition, the pre-metastatic niche, immune evasion, and enhancement of angiogenesis have been attributed to these cells. Interactions of the tumor stromal complex operate as a command and logistics center for pancreatic cancer cells, triggering and maintaining invasiveness and metastases. Understanding and modulating these interactions is a promising strategy to tame one of the most aggressive human cancers to date.