Researchers from Vanderbilt University aim to unlock how irradiation might alter the mechanical properties of the microenvironment. The study, reported in the APL Bioengineering, demonstrated that ionizing radiation can reduce the stiffness of both the extracellular matrix of an extracted tumor and an isolated matrix of collagen fibers. The results pave the way for irradiation to be used to create matrices with tailored properties.
Nearly half of all cancer patients receive radiation therapy to curb the growth of malignant cells. But little is known about how ionizing radiation affects the extracellular matrix (ECM), a patchwork of proteins and other biomolecules that surrounds cells and plays a vital role in their shape, movement and signaling functions.
"We wanted to know how radiation effects the tissues surrounding cells, particularly how this changes the stiffness of the matrix," said Cynthia Reinhart-King, an author on the paper. "The change in tissue stiffness during tumor growth can be palpable. Stiffness, for example, is what you would look for in breast self-exams."
As cancer cells grow and become increasingly dysfunctional, the network of biomolecules surrounding them are deposited more and begin cross-linking more, leading to a thicker, stiffer matrix. This tougher ECM is vital for the cancer cells to migrate throughout the body, signal to one another, and form tumors. Targeting the ECM's stiffness has become a promising tool in attacking cancer cells.
To date, much of the research on irradiation's effects on the cellular microenvironment has dealt with samples that included cells, obfuscating the irradiation's effect on just the ECM rather than the cell's internal machinery. Infrared spectroscopy revealed that the radiation does not break down individual fibers of collagen, the long, thin structural proteins that act as the matrix's scaffolding. Instead, it softens the matrix by cutting the bonds between these fibers.
Reinhart-King's team discovered that tumor cells were less likely to spread when their stiff ECMs were replaced with ECMs softened by irradiation. Cells suspended in a stiff matrix were more likely to work their way through the matrix to other side of a serum gradient, analogous to how metastasizing cancer cells break free from their tumors. Softened matrices were more likely to hold cells in place.
Reinhart-King said their findings might enable future fractionated radiation — longer term bouts of therapy using a lower intensity of radiation than most of today's therapies. One particular area of interest is determining if softening can reduce nearby blood vessel leaking and improve drug delivery.