Elucidating the Effects of Interstitial Fluid Flow on Hepatocellular Carcinoma Invasion
Thursday, May 12, 2016
1:00 PM-3:00 PM
BIOMED PhD Research Proposal
Title:
Elucidating the Effects of Interstitial Fluid Flow on Hepatocellular Carcinoma Invasion
Speaker:
Arpit Shah, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Advisor:
Adrian C. Shieh, PhD, Assistant Professor, School of Biomedical Engineering, Science and Health Systems
Abstract:
Over the last two decades with advancements in research, detection, and treatment of all cancer types in the United States, resulting in an overall 23% decrease in cancer related deaths, liver cancer has gone against this trend possessing an increased death rate. Globally, hepatocellular carcinoma (HCC), the most common form of liver cancer, ranks as the second leading cause of cancer related deaths with approximately 746,000 deaths annually. In recent years much emphasis has been placed on understanding the process of HCC cell invasion, however it has become apparent that the progression of this disease is not solely dependent on just the cancer cells or biological factors, but also their interaction with the tumor microenvironment. A significant number of studies have shown that changes in biomechanical forces within the tumor microenvironment can alter cancer progression. Previous research has demonstrated that interstitial fluid flow (IFF), one of the biomechanical forces that is altered during tumor growth, can promote cancer cell invasion. Our research serves to address the significant dearth of knowledge in understanding the effects of IFF in HCC invasion and metastasis.
The objective of this research is to examine the effects of IFF on HCC progression. In the proposed study we aim to quantify the effects of IFF on HCC cells and hepatocytes with our 3D in vitro flow invasion assay to elucidate the molecular mechanisms at play in IFF-induced HCC invasion. Additionally it has been observed in a variety of cancer types, including HCC, that the increase in matrix stiffness is a result of tumor growth, shown to disturb the mechanical forces and biochemical signaling that occurs in the microenvironment, effectively promoting disease progression. HCC also possesses a very unique disease profile and risk factors; nearly 80% of HCCs occur from patients who suffer from chronic fibrosis or cirrhosis where inflammation and hepatic wound-healing response attributes to the hepatocarcinogenesis. Chronic liver injury promotes changes in the hepatic architecture most notably with the formation of fibrotic scars and subsequently increasing matrix stiffness. Many studies have observed cellular behavior of hepatocytes and HCC cells in a stiff matrix, however none have observed synergistic effect of IFF and a stiff microenvironment in HCC cells. By modifying our 3D invasion assay we will increase the stiffness of our matrix to model a stiff microenvironment in order to study the effects of IFF. Ultimately this study will observe the effects of IFF on HCC progression by focusing on cellular invasion in a progressive HCC disease model to better understand the mechanism and signaling pathways that are involved.
In conclusion, this research will aid in uncovering the role and mechanism associated with IFF-induced HCC invasion to better understand the progression of liver cancer. Above all our study will contribute to the mounting evidence of how biomechanical forces in the tumor microenvironment influence cancer progression. For the last 20 years liver remains to be one of the only three cancer types with increasing mortality, this research will potentially identify new therapeutic targets for HCC in turn providing clinicians a better opportunity to detect, diagnose, and effectively treat liver cancer.
Contact Information
Ken Barbee
215-895-1335
barbee@drexel.edu