Influence of Glucose and Lactic Acid on Macrophage Transition in Pancreatic Tumors

Anyssa A. Rodriguez, The University of Texas Rio Grande Valley

Copyright 2023 The Author. All Rights Reserved.

Abstract

Pancreatic cancer is the seventh leading cause of cancer-related mortality worldwide. According to the American Cancer Society, it is the eleventh most common cancer diagnosed in both men and women in the United States. Pancreatic ductal adenocarcinoma (PDAC) comprises 90% of all pancreatic malignancies and is associated with poor clinical outcome because of late diagnosis and resistance to therapy. In addition, studies show that the tumor microenvironment has become an emerging interest in cancer research due to its complex components and unique characteristics that aid in cancer initiation, maintenance, and progression. Accumulating evidence signifies that tumor associated macrophages (TAMs) play a vital role in cancer progression by initiating an immunosuppressive microenvironment. In our lab, we have identified that PKD1, a serine/threonine kinase responsible for regulating multiple biological cell functions, is responsible for increasing tumorigenesis and upregulating glucose metabolism in pancreatic cancer. First, we investigated the effect that aberrant glucose metabolism had on macrophage polarization, finding that induced glucose and lactic acid conditions drove macrophages towards a pro tumorigenic phenotype. Further, we found that overexpressing PKD1 increases invasion, migration, and proliferation of KPC cells. Overexpressing PKD1 also promotes TAMs towards an M2 phenotype in KPC cells. Further analysis suggest that macrophages increase invasion, migration, and proliferation of PKD1overexpressing KPC cells. These results indicate that there is a potential relationship between PKD1 and TAMs in the tumor microenvironment that play a significant role in cancer progression.