Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes
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Paul T. Winnard Jr.1, Chi Zhang4, Farhad Vesuna1, Jeon Woong Kang5, Jonah Garry1, Ramachandra Rao Dasari5, Ishan Barman2,4, Venu Raman1,2,3
1Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
2Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
3Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA Utrecht, The Netherlands
4The Johns Hopkins University, Department of Mechanical Engineering, Whiting School of Engineering, Baltimore, MD 21218, USA
5Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Venu Raman, email: firstname.lastname@example.org
Ishan Barman, email: email@example.com
Keywords: raman spectroscopy, breast cancer, isogenic cell lines, metastases, biochemical signatures
Received: December 15, 2016 Accepted: January 17, 2017 Published: January 27, 2017
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.
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