title: Detection of lipid-rich prostate circulating tumour cells with coherent anti-Stokes Raman scattering microscopy.
abstract: BACKGROUND
  Circulating tumour cells (CTC) are an important indicator of metastasis and associated with a poor prognosis. Detection sensitivity and specificity of CTC in the peripheral blood of metastatic cancer patient remain a technical challenge.
  
  
  METHODS
  Coherent anti-Stokes Raman scattering (CARS) microscopy was employed to examine the lipid content of CTC isolated from the peripheral blood of metastatic prostate cancer patients. CARS microscopy was also employed to evaluate lipid uptake and mobilization kinetics of a metastatic human prostate cancer cell line.
  
  
  RESULTS
  One hundred CTC from eight metastatic prostate cancer patients exhibited strong CARS signal which arose from intracellular lipid. In contrast, leukocytes exhibited weak CARS signal which arose mostly from cellular membrane. On average, CARS signal intensity of prostate CTC was 7-fold higher than that of leukocytes (P<0.0000001). When incubated with human plasma, C4-2 metastatic human prostate cancer cells exhibited rapid lipid uptake kinetics and slow lipid mobilization kinetics. Higher expression of lipid transport proteins in C4-2 cells compared to non-transformed RWPE-1 and non-malignant BPH-1 prostate epithelial cells further indicated strong affinity for lipid of metastatic prostate cancer cells.
  
  
  CONCLUSIONS
  Intracellular lipid could serve as a biomarker for prostate CTC which could be sensitively detected with CARS microscopy in a label-free manner. Strong affinity for lipid by metastatic prostate cancer cells could be used to improve detection sensitivity and therapeutic targeting of prostate CTC.
authors.affiliation: Nevada Cancer Institute, One Breakthrough Way, Las Vegas, NV 89135, USA.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Mitra
authors.forename: Olivia
authors.initials: O
authors.lastname: Chao
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Urasaki
authors.forename: Oscar B
authors.initials: OB
authors.lastname: Goodman
authors.forename: Thuc T
authors.initials: TT
authors.lastname: Le
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D008853:Microscopy / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods
chemical_list: D002352:Carrier Proteins