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Macrophage-Secreted TNF? and TGF?1 Influence Migration Speed and Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways.


ABSTRACT: The ability of a cancer cell to migrate through the dense extracellular matrix within and surrounding the solid tumor is a critical determinant of metastasis. Macrophages enhance invasion and metastasis in the tumor microenvironment, but the basis for their effects is not fully understood. Using a microfluidic 3D cell migration assay, we found that the presence of macrophages enhanced the speed and persistence of cancer cell migration through a 3D extracellular matrix in a matrix metalloproteinases (MMP)-dependent fashion. Mechanistic investigations revealed that macrophage-released TNF? and TGF?1 mediated the observed behaviors by two distinct pathways. These factors synergistically enhanced migration persistence through a synergistic induction of NF-?B-dependent MMP1 expression in cancer cells. In contrast, macrophage-released TGF?1 enhanced migration speed primarily by inducing MT1-MMP expression. Taken together, our results reveal new insights into how macrophages enhance cancer cell metastasis, and they identify TNF? and TGF?1 dual blockade as an antimetastatic strategy in solid tumors. Cancer Res; 77(2); 279-90. ©2016 AACR.

SUBMITTER: Li R 

PROVIDER: S-EPMC5243269 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Macrophage-Secreted TNFα and TGFβ1 Influence Migration Speed and Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways.

Li Ran R   Hebert Jess D JD   Lee Tara A TA   Xing Hao H   Boussommier-Calleja Alexandra A   Hynes Richard O RO   Lauffenburger Douglas A DA   Kamm Roger D RD  

Cancer research 20161121 2


The ability of a cancer cell to migrate through the dense extracellular matrix within and surrounding the solid tumor is a critical determinant of metastasis. Macrophages enhance invasion and metastasis in the tumor microenvironment, but the basis for their effects is not fully understood. Using a microfluidic 3D cell migration assay, we found that the presence of macrophages enhanced the speed and persistence of cancer cell migration through a 3D extracellular matrix in a matrix metalloproteina  ...[more]

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