38. UNDERSTANDING THE PHYSICAL CUES NECESSARY FOR ECM DEGRADATION DURING CANCER MIGRATION

Department: Bioengineering
Faculty Advisor(s): Shyni Varghese

Primary Student
Name: Aereas Aung
Email: aeaung@ucsd.edu
Phone: 858-822-7920
Grad Year: 2016

Abstract
The study of cancer metastasis from the perspective of cell motility provide new insights into the intricate processes by which cancer cells invade into tissues adjacent to the tumor site. Although cancer cell migration has been touted to involve the cyclic processes of traction force generation and ECM degradation via protease activity, a quantitative understanding of the physicochemical cues initiating these events remains elusive. In this current study, we employ a novel experimental and theoretical approach to determine how these events are triggered. Specifically, we have analyzed the invasion of metastatic breast cancer cells into an ECM-based hydrogel. Our results indicate that the plastic deformation caused by the invading cells occurs due to protease activity rather than mechanical yielding of the ECM network. Furthermore, additional analyses reveal that the observed the biochemical manipulation of the ECM during cell invasion requires prerequisite physical cues. These results taken together with additional experiments suggest that protease activity during cancer cell migration requires an intracellular stress threshold to be reached.

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