Normal mammary epithelial cells promote carcinoma basement membrane invasion by inducing microtubule-rich protrusions
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Meng-Horng Lee1,2, Pei-Hsun Wu1,2, Daniele Gilkes1,2, Ivie Aifuwa1,2, Denis Wirtz1,2,3
1Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA
2Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA
3Departments of Pathology and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA
Denis Wirtz, e-mail: [email protected]
Keywords: cancer invasion, cell-cell interaction, protrusion, microtubule, laminin
Received: March 11, 2015 Accepted: July 24, 2015 Published: August 03, 2015
Recent work suggests that the dissemination of tumor cells may occur in parallel with, and even preceed, tumor growth. The mechanism for this early invasion is largely unknown. Here, we find that mammary epithelial cells (MECs) induce neighboring breast carcinoma cells (BCCs) to cross the basement membrane by secreting soluble laminin. Laminin continuously produced by MECs induce long membrane cellular protrusions in BCCs that promote their contractility and invasion into the surrounding matrix. These protrusions depend on microtubule bundles assembled de novo through laminin-integrin β1 signaling. These results describe how non-cancerous MECs can actively participate in the invasive process of BCCs.
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