Abstract 4148: Extracellular matrix biophysical properties change during nevus to melanoma progression

Abstract

Abstract Cutaneous malignant melanoma is one of the most aggressive forms of skin cancer and its major etiological risk factor is ultraviolet (UV) solar radiation. The extracellular matrix (ECM) has been shown to influence many of the hallmark characteristics of tumor development, survival, and progression across several types of cancer, including melanoma. Interactions between the tumor and the ECM often results in rearrangement, cross-linking, and deposit of specific ECM proteins, which can contribute to stiffening of the tissue and tumorigenesis. To simulate tumorigenesis, we have previously used a hepatocyte growth factor (HGF) transgenic mouse model, which develops melanoma nevii when exposed to UVB radiation. This model is highly representative of human melanoma lesions in terms of biological, genetic, and etiologic criteria. In general, microrheology involves injecting beads into a medium, tracking movement of the beads using two-photon microscopy, and using the movement to calculate the viscosity and elasticity of the medium. The physical properties of the ECM during tumorigenesis have not been well studied at the cellular level, and microrheology has rarely been used in vivo. In our in vivo microrheology study, we injected fluorescent beads into the skin of these transgenic mice. Then, we used intra-vital microscopy with particle tracking to image the beads and measure changes in ECM elasticity as nevii grow into melanoma tumors. These results, combined with transcriptomic analysis of ECM regulation and proteomic analysis of ECM signaling, could provide unique insights into components of the extracellular matrix that are involved in melanoma tumor development and offer opportunities for therapeutics to target oncogenesis. <!–EndFragment–> Citation Format: Aditya Kavuturu, Maira A. Constantino, Antonella Sassano, Glenn Merlino. Extracellular matrix biophysical properties change during nevus to melanoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4148.