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Title: Tumour-Conditioned Macrophages Up-Regulate Endothelial-Derived Fibronectin to Facilitate Lung Metastasis in Breast Cancer
Authors: LOW PIN YAN
Keywords: breast cancer, organ-specific metastasis, pre-metastatic niche, tumour-conditioned macrophages, endothelial cells, fibronectin
Issue Date: 12-Jan-2015
Citation: LOW PIN YAN (2015-01-12). Tumour-Conditioned Macrophages Up-Regulate Endothelial-Derived Fibronectin to Facilitate Lung Metastasis in Breast Cancer. ScholarBank@NUS Repository.
Abstract: Primary tumour cell-derived factors modulate distant microenvironment to become pre-metastatic niche, which is conducive for tumour homing, prior to metastasis. It is not known whether tumour secreted factors could alter endothelial function during pre-metastatic niche formation. My data revealed that lung endothelium was more susceptible to invasion by breast cancer cells, MDA-MB-231, compared to endothelium isolated from non-metastatic sites. Tumour cells disrupted the lung endothelial monolayer integrity upon adhesion and created ?gaps? on the monolayer that facilitated trans-endothelial migration. MDA-MB-231-conditioned macrophages became M2 macrophages and secreted factors (including interleukin-6) that enhanced tumour-endothelial interactions mediated by tumour-a5?1 integrins. The stimulated lung endothelium increased fibronectin expression, which is an important component of pre-metastatic niche formation. Endothelial cells from non-metastatic organs were not responsive to the tumour-conditioned macrophages. The enhanced expression of fibronectin on MDA-macrophage-primed FLEC was regulated by the activation of the JNK/cJUN and STAT3 signalling pathways.
Appears in Collections:Ph.D Theses (Open)

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