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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Gang Bao, PhD, faculty host
Summary Sentence: "Inflammation and Cancer: How are they linked?" - Cheng Dong, PhD - Pennsylvania State University
Full Summary: The Bioengineering Seminar Series is a joint seminar series between IBB and the BME department. Seminars are held on Tuesdays or Thursdays between 11am-12pm in IBB room 1128 unless otherwise indicated.
Cheng Dong, PhD - Penn State
Bioengineering Seminar Series"Inflammation and Cancer: How are they linked?"
Cheng Dong, PhD
Distinguished Professor of Bioengineering
Pennsylvania State University
Attachment of tumor cells to the endothelium (EC) under flow conditions is critical for the migration of tumor cells out of the vascular system to establish metastases. 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 dependant 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.
Melanoma cell interaction with the EC is distinct from PMN-EC adhesion in the circulation. We found PMN increased melanoma cell extravasation, which involves initial PMN tethering on the EC and subsequent PMN capture of melanoma cells and their delivery to close proximity to the EC. LFA-1 (CD11a/CD18 integrin) influenced the capture phase of PMN binding to both melanoma cells and the endothelium, while Mac-1 (CD11b/CD18 integrin) affected prolonged PMN-melanoma aggregation. Blocking Eselectin or ICAM-1 (intercellular adhesion molecule) on the endothelium or ICAM-1 on the melanoma surface reduced PMN-facilitated melanoma extravasation. Results indicate a novel finding that PMN-facilitated melanoma cell arrest on the EC is modulated by the hydrodynamic shear rate that affects the on-rate (kon) adhesion kinetic constant in PMN-melanoma cell aggregations; rather than by the flow shear stress which is the force exerted on formed adhesion bonds. 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. Functional blocking of the IL-8 receptors CXCR1 and CXCR2 on PMNs, or neutralizing soluble IL-8 in cell suspensions, significantly decreased the level of Mac-1 up-regulation on PMNs while in communicating with melanoma cells and reduced melanoma extravasation. We also found that activation of nuclear factor of B (NF-B) in PMNs is responsible for endogenous IL-8 production in response to melanoma microenvironment. These results provide new evidence for the complex role of hemodynamic forces, secreted chemokines, and PMN-melanoma adhesion in the recruitment of metastatic cancer cells to the endothelium in the microcirculation, which are significant in fostering new approaches to cancer treatment through anti-inflammatory therapeutics. (This work was supported by NIH CA-125707 and NSF CBET 0729091.)
