Gap junction coupling is required for tumor cell migration through lymphatic endothelium

Arteriosclerosis, Thrombosis, and Vascular Biology
Natalie O Karpinich, Kathleen M Caron

Abstract

The lymphatic vasculature is a well-established conduit for metastasis, but the mechanisms by which tumor cells interact with lymphatic endothelial cells (LECs) to facilitate escape remain poorly understood. Elevated levels of the lymphangiogenic peptide adrenomedullin are found in many tumors, and we previously characterized that its expression is necessary for lymphatic vessel growth within both tumors and sentinel lymph nodes and for distant metastasis. This study used a tumor cell-LEC coculture system to identify a series of adrenomedullin-induced events that facilitated transendothelial migration of the tumor cells through a lymphatic monolayer. High levels of adrenomedullin expression enhanced adhesion of tumor cells to LECs, and further analysis revealed that adrenomedullin promoted gap junction coupling between LECs as evidenced by spread of Lucifer yellow dye. Adrenomedullin also enhanced heterocellular gap junction coupling as demonstrated by Calcein dye transfer from tumor cells into LECs. This connexin-mediated gap junction intercellular communication was necessary for tumor cells to undergo transendothelial migration because pharmacological blockade of this heterocellular communication prevented the ability of tumo...Continue Reading

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May 28, 2016·BMC Cell Biology·Jean X Jiang, Silvia Penuela
Feb 14, 2019·Cellular and Molecular Life Sciences : CMLS·Harish P Janardhan, Chinmay M Trivedi
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Apr 8, 2020·ACS Pharmacology & Translational Science·Claire E Trincot, Kathleen M Caron

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