Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes

// Paul T. Winnard Jr. 1 , Chi Zhang 4 , Farhad Vesuna 1 , Jeon Woong Kang 5 , Jonah Garry 1 , Ramachandra Rao Dasari 5 , Ishan Barman 2, 4 , Venu Raman 1, 2, 3 1 Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 2 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 3 Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA Utrecht, The Netherlands 4 The Johns Hopkins University, Department of Mechanical Engineering, Whiting School of Engineering, Baltimore, MD 21218, USA 5 Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Correspondence to: Venu Raman, email: vraman2@jhmi.edu Ishan Barman, email: ibarman@jhu.edu Keywords: raman spectroscopy, breast cancer, isogenic cell lines, metastases, biochemical signatures Received: December 15, 2016      Accepted: January 17, 2017      Published: January 27, 2017 ABSTRACT Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker. Decision algorithms derived from the Raman spectra unambiguously identified these isogenic cell lines as unique biological entities – a finding reinforced through metabolomic analyses that indicated tissue of origin metabolite distinctions between the cell lines. Notably, complementarity of the metabolomics and Raman datasets was found. Our findings provide evidence that metastatic spread generates tissue-specific adaptations at the molecular level within cancer cells, which can be differentiated with Raman spectroscopy.