4:10 pm to 5:00 pm
Biomechanics in Cancer and Inflammation
Recent studies have illustrated a complex role of hydrodynamic shear flow, secreted inflammatory chemokines by a tumor microenvironment, and interactions of immune cells with circulating tumor cells in the recruitment of metastatic cancer cells to the vascular endothelium (EC). These studies are significant in fostering new approaches to cancer treatment through anti-inflammatory therapeutics.
Attachment of tumor cells to the EC under flow conditions is critical for the migration of tumor cells out of the vascular system to establish metastases in tissues. The interactions between cancer cells and the host immune system are of particular interest to our group. Innate immune system processes can potentially promote tumor progression through inflammation-dependent mechanisms.
Human neutrophils (PMNs), which comprise 50-70% of circulating leukocytes, are being studied to better understand how the host immune system affects cancer cell adhesion and subsequent migration and metastasis. We have also studied how increased plasma fibrin levels affect cancer cell adhesion especially in association with immune cells activation due to tumor microenvironment-mediated thrombin, a serine protease that converts normal fibrinogen into fibrin.
As a model, we have studied melanoma cells and the dynamic adhesion to the EC under flow conditions, which is distinct from PMN-EC adhesion in the circulation. We found PMN increased melanoma cell adhesion and extravasation, which involves shear-dependent initial PMN tethering on the EC and capturing melanoma cells in a close proximity to the EC. In addition, melanoma-induced inflammatory cytokine IL-8 contributes to PMN tethering and subsequent melanoma arrest on the EC via the PMN-melanoma cell binding. Tumor cell adhesion to the EC induces endothelial junction breakdown that results in circulation-mediated tumor cell metastasis. These studies present a platform for studying the biomechanics in cancer and inflammation.
Professor Cheng Dong graduated in 1982 with an undergraduate major in Engineering Mechanics from Shanghai Jiao-Tong University, Prof. Dong received his Ph.D in Engineering Science in 1988 from Columbia University. He is now a Distinguished Professor of Biomedical Engineering and Head of the Penn State Department of Biomedical Engineering.
Prof. Dong is currently a Member of the United States National Committee on Biomechanics (USNCB); a Fellow of the Biomedical Engineering Society (BMES); a Fellow of the American Institute of Medical and Biological Engineering (AIMBE); a Council Member of the International Society of Biorheology (ISB); a Chair of the BMES Cellular & Molecular Bioengineering (CMBE) Special Interest Group (SIG); and an immediate-past Secretary of the national Biomedical Engineering/Bioengineering Council of Chairs (CoC). He is an active Member of the American Association for Cancer Research (AACR) and the American Physiological Society (APS). Dr. Dong is currently an Associate Editor for BMES Cellular and Molecular Bioengineering; and an Associate Editor for Molecular and Cellular Biomechanics; as well as an Editorial Member of the Chinese Journal of Medical Biomechanics. He was also a past Associate Editor for BMES Annals of Biomedical Engineering; ASME Journal of Biomechanical Engineering; and ASME Journal of Medical Devices. Prof. Dong has received several awards, including the US National Science Foundation (NSF) Faculty Career Award, American Cancer Society Faculty Research Award, ASME Y.C. Fung Young Investigator Award, BMES Harold Lamport Young Investigator Award, ASME Melville Medal, and ASME Best Journal Paper Award.
The major focus of Dr. Dong’s research is to elucidate biomechanical, biophysical and biochemical aspects of cellular function in the circulatory systems, with particular interest in cellular biomechanics, cell adhesion, cell migration, cell signaling, systems biology, and multi-scale modeling of biological systems. Current research at Penn State includes studies of micro-hemodynamics, leukocyte rheology, intercellular and intracellular signaling, cancer immunology and metastases. In particular, he is investigating how fluid dynamics, coagulation, protein and cell signaling, and tumor microenvironment change leukocyte and/or endothelial immune functions, which affect tumor cell extravasation in the microcirculation and subsequent metastasis.