Abstract A84: Intravital microscopy reveals biopsy induced local wound-healing response

2015 
A biopsy is for most types of cancer the golden standard for a definitive cancer diagnosis, as it provides the most accurate analysis of tissues. However taking biopsies creates a wound thereby potentially changing the composition and architecture of the tissue. In non-pathological situations, wounded tissue ‘repairs’ itself by a cascade of cellular events, including the induction of an inflammatory response that promotes cell proliferation and migration of surrounding cells to close the wound. Proliferation and migration are two malignant processes that promote tumor progression and metastatic disease. Thus it is vital to identify the potential effect of biopsy on the behavior of cells that remain in the tumor. By making use of repeated high-resolution intravital microscopy (IVM) we studied how the behavior of tumor cells locally changes upon biopsy. Our results showed that biopsy-like injury triggers a wound-healing response observed as increased tumor cell migration and proliferation. 24 hours after biopsy-like injury there was a 1.75 fold increase in migratory cells and a 1.52 fold increase in proliferating cells compared to the control group that did not received an injury. IVM showed that the observed effects were mediated by a CCL-2- dependent inflammation response. Interestingly, immune cell ablation by dexamethasone, a glucocorticoid commonly used to prevent inflammation resulted in decreased tumor cell motility and proliferation and suppressed the observed wound healing response. This result opens new therapeutic possibilities to prevent biopsy undesired effects on tumor cell behavior. Taken together, our data show that biopsy induces a local wound-healing response in the tumor through an immune system mediated mechanism and illustrate that IVM is a powerful technique to study local and temporal changes in cell behavior that cannot be assessed by other techniques (e.g. immunohistochemistry) that only provide a snapshot of a dynamic tissue. Furthermore this tool can be useful to determine local and dynamic responses of (tumor) cells to other more aggressive clinical interventions, such as surgical resection or chemotherapeutic treatment. Citation Format: Maria Alieva, Burcin Colak, Carla Boquetale, Jacco Van Rheenen. Intravital microscopy reveals biopsy induced local wound-healing response. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A84.
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