Flipping the switch on tumor growth

Pictures of angiogenic tumor cells
Time-lapse imaging can reveal tell-tale changes in cellular behaviors associated with tumor growth.

Without a blood supply, a tumor can remain dormant and harmless. But new blood vessel growth from an existing vessel, a process called angiogenesis, is a hallmark of both benign and malignant tumors. During angiogenesis, blood vessels invade tumors and activate them, fueling their growth.

Now, Marsha A. Moses, PhD, who directs the Vascular Biology Program at Boston Children’s Hospital, and members of her laboratory have revealed that a specialized imaging system can detect changes in cell behaviors. These changes predict when tumors are leaving a state of dormancy and becoming more likely to grow.

“Can we revert an activated tumor back to its dormant state?” asks Peng Guo, PhD, a researcher in Moses’s lab, an instructor in surgery at Harvard Medical School and co-first author of the paper. “The ultimate dream would be to detect when that ‘angiogenic switch’ has flipped and start treatment with non-toxic therapies as soon as possible.”

Until now, methods to identify this switch have been time and labor intensive and require expensive reagents and instrumentation.

“We wanted to conduct a visual, economical and quantitative analysis of tumor cells to determine whether or not we could distinguish between dormant and active states,” says Moses, who was senior author on the paper. Their findings were published in the Journal of the International Society for Advancement of Cytometry.

A new movement in tumor monitoring?

Moses and her team turned to quantitative phase imaging (QPI): they placed wells of cell cultures underneath a microscope and recorded them in time-lapse. From these images, taken every five minutes over a period of 48 hours, the team did a pixel-by-pixel analysis of the cells’ migration, motility, thickness, volume, proliferation rate and several other factors.

“Using cancer cells, we discovered that we could, in fact, identify changes in cells’ movement that are associated with a tumor’s escape from dormancy,” says Moses.

Graph showing migration patterns of tumor cells
Cell migration trajectories of angiogenic (A) and non-angiogenic tumor cells (B) measured over a period of six hours, plotted from their point of origin (0, 0). Each line represents an individual cell. Angiogenic cells have higher migratory behavior.

“We found that angiogenic cells have significantly greater thicknesses, smaller cell areas and higher motility speeds than dormant cells,” says Jing Huang, PhD, a researcher in Moses’ lab and a co-first author of the paper.

Although still far away from being ready for the clinic, QPI presents a novel method for continuously, efficiently and non-invasively monitoring tumor cells for activation. Moses and her team envision that QPI, in combination with clinical biomarker staining, could one day be used to characterize the percentage of angiogenic and non-angiogenic cells in a given tumor.

“Our hope is that one day, this technology can provide useful clinical information that could be used to guide personalized therapies based on someone’s precise tumor phenotype,” says Huang.

“We are committed to understanding the mechanisms underlying tumor dormancy and leveraging that data in innovative ways, with the eventual goal of making maximum clinical impact,” says Moses.