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Publication - Professor Paul Martin

    Proteolytic and opportunistic breaching of the basement membrane zone by immune cells during tumour initiation

    Citation

    Berg, MVD, MacCarthy-Morrogh, L, Carter, D, Morris, J, Bravo, IR, Feng, Y & Martin, P, 2019, ‘Proteolytic and opportunistic breaching of the basement membrane zone by immune cells during tumour initiation’. Cell Reports.

    Abstract

    Cancer-related inflammation impacts significantly on cancer development and
    progression. From early stages, neutrophils and macrophages are drawn to pre-neoplastic cells in the epidermis, but before directly interacting, they must first breach the underlying extracellular matrix barrier layer which includes the basement membrane. Using several different skin cancer models and a newly established collagen I-GFP transgenic zebrafish line we have undertaken Correlative Light and Electron Microscopy (CLEM) to capture the moments
    when immune cells traverse the basement membrane. We show evidence both for active proteolytic burrowing, and for the opportunistic use of preexisting weak spots in the matrix layer. We show that these small holes, through to much larger, cancer cell generated or wound-triggered gaps in the matrix barrier, provide portals for immune cells to access cancer cells in the epidermis and thus are rate limiting in cancer progression.

    Full details in the University publications repository