Role of the mechanical microenvironment on CD-44 expression of breast adenocarcinoma in response to radiotherapy

Abstract

The biological effects of ionizing radiation are exploited in the clinical practice of radiotherapy to destroy tumour cells while sparing the surrounding normal tissue. While most of the radiotherapy research focused on DNA damage and repair, recently a great attention is going to cells' interactions with the mechanical microenvironment of both malignant and healthy tissues after exposure. In fact, the stiffness of the extracellular matrix can modify cells' motility and spreading through the modulation of transmembrane proteins and surface receptors' expression, such as CD-44. CD-44 receptor has held much interest also in targeted-therapy due to its affinity with hyaluronic acid, which can be used to functionalize biodegradable nanoparticles loaded with chemotherapy drugs for targeted therapy. We evaluated changes in CD-44 expression in two mammary carcinoma cell lines (MCF10A and MDA-MB-231) after exposure to X-ray (2 or 10 Gy). To explore the role of the mechanical microenvironment, we mimicked tissues' stiffness with polyacrylamide's substrates producing two different elastic modulus values (0.5 and 15 kPa). We measured a dose dependent increase in CD-44 relative expression in tumour cells cultured in a stiffer microenvironment. These findings highlight a crucial connection between the mechanical properties of the cell's surroundings and the post-radiotherapy expression of surface receptors.