Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases

In this study, we show how differential expression of a network of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis. Attenuating HMMR in LUAD cells diminished their ability to initiate lung tumors and distant metastases. HMMR upregulation was not required for dissemination in vivo, but enhanced ECM-mediated signaling, LUAD cell survival, and micrometastasis expansion in hyaluronan-rich microenvironments in the lung and brain metastatic niches. Our findings reveal an important mechanism by which disseminated cancer cells can coopt the inflammatory ECM to persist, leading to brain metastatic outgrowths. Cancer Res; 77(8); 1905–17. ©2017 AACR.

Source: Cancer Research - April 13, 2017 Category: Cancer & Oncology Authors: Laura E. Stevens, William K.C. Cheung, Sally J. Adua, Anna Arnal–Estape, Minghui Zhao, Zongzhi Liu, Kelly Brewer, Roy S. Herbst, Don X. Nguyen Tags: Microenvironment and Immunology Source Type: research