Ithaca, N.Y.— Michael King is going to trick the cancer cells into showing him how they work.
An associate professor at Cornell, King heads a lab focused on cell adhesion. He is one of a group of scientists across the country who are using nanotechnology, the manipulation of particles as small as molecules, to investigate how and why cancer cells in the bloodstream adhere to blood vessel walls.
While the phenomenon may sound highly specific, King’s quest tackles a broader question about the process by which cancers – especially the breast and prostate varieties – can metastasize. In order for many tumors to form, a cancer cell has to attach itself to the wall of a blood vessel, where it will escape the bloodstream to feed and grow.
Floating through veins and arteries, the cells won’t be nourished and will eventually die. It’s a simple enough idea, but the process is complicated by invisible biological material too little understood.
“What are the important proteins?” King asks. “How does it depend on things like the blood flow and the concentration of cells?”
To investigate these questions, his lab grows cancer cells and runs them through thin plastic tubes at the same speed as blood running through blood vessels. To more closely resemble the inner surface of a blood vessel, King coats them with nanoparticles to better replicate the actual tissue.
When materials are the size of atoms they often display remarkable characteristics like solubility, strength and conductivity that make them compelling to a broad array of scientists and industries. In King’s lab nano-sized materials are used to simulate the inside of the body in experiments and as a method for delivering genetic material to cells.
A reporter visited King’s lab during a blizzard, so activity was slow. Dr. King, a ruddy man with a penchant for sweater vests, bantered with the graduate students who’d made it in. They were looking through high-powered microscopes laid out next to computers on lab benches. There were a few machines which looked like computer printers but are actually used for measuring and testing cell activity.
In a video animation of one of the lab’s experiments it’s possible to see how healthy blood cells race through the tubes while the cancer cells roll slowly along the vessel walls, abetted by a protein called selection which enables the cells to take root. (Click on the video at the top of the story.)
Alex Halperin Photo
“If we can learn how this process works,” said King (pictured), “we can potentially disrupt it.”
The experiment employs computer science to design models as well as physics and engineering to better “understand how fluids flow and apply their forces on microscopic cells.”
King’s project is one of three at Cornell and Weill Cornell Medical College looking at cancer under the Physical Sciences Oncology Centers (PSOC), a National Institutes of Health initiative that funds scientists from a broad range of sub-fields to train their expertise on cancer. Another examines how tumors attract new blood vessels while the third looks at cell migration. Together, the projects employ physical sciences to look at how cells grow, migrate and implant themselves to begin the process again.
Bringing physical scientists into the “race for the cure” – or at least for a greater understanding of cancer writ-large – is a recent preoccupation of oncology. Cornell is one of 12 PSOC locations. The idea is that physicists, chemists and other specialists bring different questions and problem-solving approaches to the disease.
An expert in fluid mechanics and mathematical modeling, for example, might bring a fresher perspective to cancer than doctors, cell biologists and others more professionally habituated to the fight against cancer. As King, whose own degrees are in chemical engineering, says of “outsider” scientists, “We’re not encumbered with an exhaustive knowledge of cancer dogma.”
Larry Nagahara, program director of the national PSOC project, said a physicist might ask “How much energy does it take for a cancer cell to move from a tumor to another site?”
Across the scientific spectrum, researchers are increasingly focused on the ultra-small, which makes nanotechnology’s scientific techniques for manipulating material as small as molecules a valuable contribution to those efforts. Additional projects incorporate tools and devices only a bit larger than the nanoscale, particles often defined as smaller than 100 nanometers, the equivalent of one ten millionth of a meter.
At the Massachusetts Institute of Technology a PSOC directed by Dr. Scott Manalis hopes to incorporate tools used in nanotech research to determine new ways to measure cells, such as their weight. Such research could eventually be applied to cancer diagnostics or therapies.
In a separate Cornell experiment, King’s lab is investigating how to use nanosized materials known as liposomes to deliver siRNA, a genetic material capable of disrupting cellular activity. Breakthroughs here might let him control, in those nano-coated tubes, the anchoring or survival of cancer cells in blood vessels.
The King lab is also investigating the use of halloysite, naturally occurring nanoparticles which can be found in the ground “in the Utah desert and someplace in Russia.” King became familiar with the material from a Rochester N.Y.-based company called NaturalNano which is using them to strengthen materials found in common consumer goods. One advantage of them being natural is that they’re less likely to upset consumers worried about health risks associated with nanoscale materials.
But the work is not cheap. These experiments employ equipment like a particle sizer and counter. “It generates a histogram of the cells or particles or whatever you feed through there. It’s a very accurate way to tell the size distribution of particles.”
The cost for the counter alone? About $30,000.