Can Physics Cure Cancer?

CBR member and Assistant Professor Evgeniy Khain, of the Department of Physics, uses physics to understand the growth of tumors. In particular, he uses mathematical models to predict and understand the basic mechanisms by which cancer cells migrate and spread. In the March 2011 issue of the journal Physics Review E, Khain and his collaborators published “Collective Behavior of Brain Tumor Cells: The Role of Hypoxia,” (Volume 83, Article number 031920). The introduction, reproduced in part below (without all the citations), describes clearly the goal of the study.

“Collective behavior of living cells is an intriguing and challenging phenomenon not only from the biological perspective, but also from the physical point of view. This explains an increasingly growing interest about this subject in the physics community. A remarkable range of collective behavior is displayed in morphogenesis, wound healing, and tumor growth. In the present study, we focus on the invasion of aggressive malignant brain tumors.

Gliomas are the most common type of primary brain tumors. A hallmark of malignant gliomas is their ability to invade into surrounding brain tissue. Glioma cells not only proliferate (divide), but detach from the tumor core and actively migrate away into the extracellular matrix. Therefore, surgery is commonly noncurative as cells invade the brain and escape resection. The invasive nature of malignant brain tumors often leads to recurrence: formation of distant recurrent (secondary) tumors in the invasive region. Experimental observations show that cells on the surface of a primary tumor (so-called proliferative cells) divide much more frequently than individual invasive cells. However, invasive cells might form clusters, which can eventually develop into secondary tumors….

The main focus of the present work is on an intriguing question: How does hypoxia (lack of oxygen) affect cell behavior? Cells inside a primary brain tumor are regularly subjected to hypoxic conditions. It is well known that hypoxia leads to increased tumor invasion; however, the mechanism of this phenomenon remains unclear. How do hypoxic conditions affect cell motility, cell proliferation, and cell-cell adhesion? We investigated these problems both experimentally and theoretically; we further confirmed our theoretical predictions in additional experiments."

The coauthors on the paper include Scott Hopkins and Alexandra Szalad who both obtained a masters in physics at Oakland, Mark Katakowski who graduated in 2005 with a PhD in Biomedical Sciences: Medical Physics, and Distinguished Professor Michael Chopp, and other members of Chopp’s laboratory at Henry Ford Hospital. The study represents an elegant comparison of Khain’s mathematical model and Chopp’s experiments. They write

“Theoretical modeling is successful when it not only describes the existing experimental observations, but also can produce an experimentally testable hypothesis. One of the main theoretical predictions of our model is that the strength of cell-cell adhesion decreases due to hypoxia. To test this hypothesis, we performed a Western blot to measure expression of E-cadherin, an important transmembrane protein that positively regulates the strength of cell-cell adhesion… Our western blot experiments showed a clear down-regulation of E-cadherin 24 hours after cells had been placed under hypoxic conditions. This finding clearly confirms our theoretical prediction.”