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

van den Berg, Maaike C.W., MacCarthy-Morrogh, Lucy, Carter, Deborah, Morris, Josephine, Ribeiro Bravo, Isabel, Feng, Yi and Martin, Paul 2019. Proteolytic and opportunistic breaching of the basement membrane zone by immune cells during tumor initiation. Cell Reports 27 (10) , 2837-2846.e4. 10.1016/j.celrep.2019.05.029

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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 that includes the basement membrane. Using several different skin cancer models and a 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 pre-existing weak spots in the matrix layer. We show that these small holes, as well as 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 2211-1247
Date of First Compliant Deposit: 11 June 2019
Date of Acceptance: 7 May 2019
Last Modified: 12 Jun 2019 10:56

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