097 Epidermal integrin α3β1 is a regulator of cytokine, CSF-1, and of crosstalk from keratinocytes to dermal macrophages

As the major cell surface receptors for extracellular matrix, integrins regulate adhesion and migration, have been shown to drive tumor growth progression. Our earlier findings identified integrin α3β1 as a key regulator of keratinocyte secretome skin microenvironment, indicating its potential efficacy therapeutic target. Previous mass spectrometric analysis conditioned medium from immortalized keratinocytes indicated that positively regulates colony-stimulating factor 1 (CSF-1), secreted cytokine is primary macrophage differentiation, proliferation, survival. In our current studies, we first validated CSF-1 in vitro, well two cutaneous remodeling contexts vivo: tumorigenesis wound healing, using epidermis-specific α3 knockout mice. Additionally, previously number tumor-associated macrophages were reduced stroma following deletion epidermal cells, citing an increase apoptosis. Consistently, co-culture study used RAW 264.7 demonstrate proliferation when cultured media by lack compared α3β1-expressing keratinocytes. Overall, data indicate on expression CSF-1, crosstalk likely impact population wounds tumors.