Clinical doses of radiation reduce collagen matrix stiffness

Abstract

Cells receive mechanical cues from their extracellular matrix (ECM), which direct migration, differentiation, apoptosis, and in some cases, the transition to a cancerous phenotype. As a result, there has been significant research to develop methods to tune the mechanical properties of the ECM and understand cell-ECM dynamics more deeply. Here, we show that ionizing radiation can reduce the stiffness of an ex vivo tumor and an in vitro collagen matrix. When non-irradiated cancer cells were seeded in the irradiated matrix, adhesion, spreading, and migration were reduced. These data have ramifications for both in vitro and in vivo systems. In vitro , these data suggest that irradiation may be a method that could be used to create matrices with tailored mechanical properties. In vivo , these suggest that therapeutic doses of radiation may alter tissue mechanics directly.

Diffusion model comparison identifies distinct tumor sub‐regions and tracks treatment response

“…Although further work is needed to understand its relationship with tumor microstructure, may itself be a useful biomarker, with the observed increase suggesting that radiotherapy has an influence on the extracellular space. Single and fractionated radiotherapy doses have previously been shown to affect the extracellular matrix, causing a reduction in collagen matrix stiffness . This reduction in stiffness, however, was not associated with a change in the collagen architecture, a microstructural property that may be hypothesized to have sensitivity to.…”

Significance of skull osteoporosis to the development of peritumoral brain edema after LINAC-based radiation treatment in patients with intracranial meningioma

“…Previous studies described that irradiation affects collagen structure and can lead to collagen changes and damage [24,25]. When the meningioma is not treated with surgery or radiation therapy, tumor growth is the primary cause of damage to the tumor-brain contact interface including the arachnoid trabeculae.…”

Tumour Initiation: a Discussion on Evidence for a “Load-Trigger” Mechanism

“…(ii) Radiation : Radiation may reduce ECM stiffness partly by eliciting cleavage of peptide bonds in the backbone of the collagen polymer. It has been proposed that collagen in aged individuals will have accumulated damage, including single bond cleavage events, thereby causing changes in the collagen primary structure resulting in destabilisation of the collagen architecture [100, 101]. (iii) Inflammation : The persistence of inflammation at the injury site sustains ECM disorganization, including that of collagen, partly by activating MMPs.…”

“…In this regard speculative suggestions have been made on the possibility of pharmacologically altering activity in the ECM of, for example, LOX [118], CCN1 [119], fibronectin [64] or FAK [120], which may provide accessible targets. Intriguingly, it has been suggested [101] that their studies indicated that therapeutic radiation may be used to beneficially modify ECM mechanical properties. Further, mechanical signals, including tension, compression, and paper taping may be effective in targeting the development of a fibrotic ECM [121].…”