Pancreatic cancer is the product of microenvironment alterations which emerge from inflammatory signaling and progress to more devastating cases such as Pancreatic Ductal Adenocarcinoma (PDAC). PDAC is extremely aggressive with a statistical five-year survival rate of merely 3%-5%, and is more than relevant to cancer research being that it is the fourth leading cause of cancer-related deaths in the US. Unfortunately pancreatic cancer is often unnoticed until reaching its hardly treatable end stages, which perpetuates the low survival rate.
The onset of PDAC may be facilitated by the activation of pancreatic stellate cells (PSCs), which secrete collagen and markedly contribute to tissue fibrosis. Inflammatory factors and activation of PSCs are hallmarks of pancreatitis and could increase occurrence rates of pancreatic cancer.
The purpose of this thesis is to elucidate inflammatory signaling patterns starting with the onset of acute pancreatitis and through future studies of the more damaging states of chronic pancreatitis and cancer progression. Through the induction of acute pancreatitis in oncogenic and wild type mouse models and evaluating cytokine expression levels via RT-PCR a link between inflammatory signaling and disease state progression will be delineated. This model utilizes mice with mutant KRas, a gene activated in nearly all PDAC incidences, and constitutively active Akt, an oncogene activated in nearly all cancers. Preliminary results indicate that when experimentally inducing pancreatitis in mice predisposed to pancreatic cancer tissue remodeling and leukocyte infiltration is observed as a result of cytokine expression. Furthermore, macrophage and neutrophil stains are positive with one round of cerulein injections proving that acute inflammation is induced by these methods.
Pancreatitis is a risk factor for pancreatic cancer which can be caused by environmental factors including smoking, alcohol consumption, and obesity. By understanding the mechanism by which inflammation occurs and the cytokine signaling involved we can attempt inhibit tumor-promoting signaling pathways in the pancreas stroma.
Altomare, Deborah A.
Bachelor of Science (B.S.)
College of Medicine
Orlando (Main) Campus
Length of Campus-only Access
Cline, Kathryn, "Microenvironment Changes in the Pancreatic Stroma Induced by Inflammation" (2016). Honors in the Major Theses. 104.