How gastrin-releasing peptide receptor (GRPR) and αvβ3 integrin expression reflect reorganization features of tumors after hyperthermia treatments

The outcome of tumor treatment via hyperthermia in the clinic has been reported to be heterogeneous. Here, we assessed how the presence of gastrin-releasing peptide receptor (GRPR) and alpha(v)beta(3) integrin together with the morphology of the vascularization reflects the growth behavior of tumors after hyperthermia treatment. MDA-MB-231 tumor bearing mice were treated either with high (46 degrees C) or low dose (42 degrees C) water hyperthermia for 60 min. Changes of GRPR and alpha(v)beta(3) integrin expression were assessed via multiplexed optical imaging. Vascularization was reconstructed and quantified by mu CT imaging after contrast agent injection. We found that high dose hyperthermia is capable of increasing the expression of GRPR, alpha(v)beta(3) integrin, CD31, and Ki67 in tumors. Also the morphology of tumor vasculature changed (increased relative blood volume and small-diameter vessel density, decreased expression of alpha-SMA). Low dose hyperthermia induced comparatively moderate effects on the investigated protein expression pattern and vascular remodeling. We conclude that under defined circumstances, specific temperature doses affect the reorganization of tumor regrowth, which is triggered by residual "dormant" cells even though tumor volumes are transiently decreasing. Further on, GRPR, alpha(v)beta(3) integrin expression are versatile tools to surveil potential tumor regrow during therapy, beyond the conventional determination of tumor volumes.