title: Extracellular Matrix Receptor Expression in Subtypes of Lung Adenocarcinoma Potentiates Outgrowth of Micrometastases.
abstract: Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. 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 disseminationin 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.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Stevens
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: William K C
authors.initials: WKC
authors.lastname: Cheung
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Adua
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Anna
authors.initials: A
authors.lastname: Arnal-Estapé
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Kelly
authors.initials: K
authors.lastname: Brewer
authors.affiliation: Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut.|Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut. don.nguyen@yale.edu.|Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Don X
authors.initials: DX
authors.lastname: Nguyen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D061206:Neoplasm Micrometastasis; D059467:Transcriptome; D059016:Tumor Microenvironment
chemical_list: D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor