title: Label-Free Raman Spectroscopy Detects Stromal Adaptations in Premetastatic Lungs Primed by Breast Cancer.
abstract: Recent advances in animal modeling, imaging technology, and functional genomics have permitted precise molecular observations of the metastatic process. However, a comprehensive understanding of the premetastatic niche remains elusive, owing to the limited tools that can map subtle differences in molecular mediators in organ-specific microenvironments. Here, we report the ability to detect premetastatic changes in the lung microenvironment, in response to primary breast tumors, using a combination of metastatic mouse models, Raman spectroscopy, and multivariate analysis of consistent patterns in molecular expression. We used tdTomato fluorescent protein expressing MDA-MB-231 and MCF-7 cells of high and low metastatic potential, respectively, to grow orthotopic xenografts in athymic nude mice and allow spontaneous dissemination from the primary mammary fat pad tumor. Label-free Raman spectroscopic mapping was used to record the molecular content of premetastatic lungs. These measurements show reliable distinctions in vibrational features, characteristic of the collageneous stroma and its cross-linkers as well as proteoglycans, which uniquely identify the metastatic potential of the primary tumor by recapitulating the compositional changes in the lungs. Consistent with histological assessment and gene expression analysis, our study suggests that remodeling of the extracellular matrix components may present promising markers for objective recognition of the premetastatic niche, independent of conventional clinical information. Cancer Res; 77(2); 247-56. ©2016 AACR.
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Paidi
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Rizwan
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.|Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Menglin
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.|The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ishan
authors.initials: I
authors.lastname: Barman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D015674:Mammary Neoplasms, Animal / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology*; D012815:Signal Processing, Computer-Assisted; D013059:Spectrum Analysis, Raman / Q000379:methods*; D059016:Tumor Microenvironment / Q000502:physiology