The Role Of Microenvironment In The Development Of Pancreatic Ductal Adenocarcinoma

The initiation and progression of cancer are closely related to its microenvironment. How to restrict or eliminate cancer by using the interaction of tumor and its microenvironment has become a new direction for cancer prevention and treatment. The research of pancreatic ductal adenocarcinoma (PDAC) microenvironment, which is extremely rich in sorts of components, is still in the initial phase. In present study, the main pathological changes in fibrous mass-forming chronic pancreatitis (FMCP) and PDAC microenvironment were observed and further compared via Semi-quantitative method;Expression of fibroblast activation protein ( FAP) and stromal cell-derived factor 1 (SDF-1) in human PDAC tissue and cell lines were detected using immunohistochemistry (IHC) and western blotting, following which the correlation between FAP expression and clinicopathological parameters or prognosis were evaluated ; The proportion of myeloid-derived suppressor cells (MDSC) in human peripheral blood mononuclear cells (PBMC) was detected by flow cytometry, while IHC was performed for FOXP3 expression in human PDAC tissue;Orthotopic nude mice model of PDAC by injection of human PDAC cell lines, orthotopic model of PDAC by injection of human PDAC cell line on CP nude mouse model, orthotopic model of PDAC by injection of human PDAC cell line on mouse with reduced immunity and model of human PDAC xenografts in severe combined immunodeficiency (scid) mouse were build attempting to establish an in vivo platform for PDAC microenvironment research. As a result, pathological changes in FMCP and PDAC microenvironment were very similar;Tumor cells of PDAC was capable of expressing FAP and SDF-1 and FAP expression was closely related to prognosis;The proportion of MDSC in PBMC of PDAC patient increased obviously, but decreased significantly after the surgery. In addition, the number of lymphocytes in PDAC which expressed FOXP3 was significantly increased; Seventeen transplantable xenografts were established (48.5%), and their histologic and biological characterization showed close similarity to the original cancers. In conclusion, FMCP and PDAC were closely related and FMCP might provide a favorable microenvironment for PDAC to develop; PDAC involved in promoting desmoplasia directly possibly through autocrine stromal-associated protein and FAP may be an ideal target for PDAC therapy;MDSC had close relationship with PDAC and possibly through induction of regulatory T cells (Treg) involved in the process of immune escape; Transplantation of human PDAC xenografts in scid mouse was a more feasible way in current to establish an in vivo platform for PDAC microenvironment. The aim of present study is to provide possible research direction and in vivo research platform for PDAC microenvironment.