Optical quantification of cellular mass, volume, and density of circulating tumor cells identified in an ovarian cancer patient

Kevin G. Phillips, Carmen Ruiz Velasco, Julia Li, Anand Kolatkar, Madelyn Luttgen, Kelly Bethel, Bridgette Duggan, Peter Kuhn, Owen J.T. McCarty

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Clinical studies have demonstrated that circulating tumor cells (CTCs) are present in the blood of cancer patients with known metastatic disease across the major types of epithelial malignancies. Recent studies have shown that the concentration of CTCs in the blood is prognostic of overall survival in breast, prostate, colorectal, and non-small cell lung cancer. This study characterizes CTCs identified using the high-definition (HD)-CTC assay in an ovarian cancer patient with stage IIIC disease. We characterized the physical properties of 31 HD-CTCs and 50 normal leukocytes from a single blood draw taken just prior to the initial debulking surgery. We utilized a non-interferometric quantitative phase microscopy technique using brightfield imagery to measure cellular dry mass. Next we used a quantitative differential interference contrast microscopy technique to measure cellular volume. These techniques were combined to determine cellular dry mass density. We found that HD-CTCs were more massive than leukocytes: 33.6 ± 3.2 pg (HD-CTC) compared to 18.7 ± 0.6 pg (leukocytes), p < 0.001; had greater volumes: 518.3 ± 24.5 fL (HD-CTC) compared to 230.9 ± 78.5 fL (leukocyte), p < 0.001; and possessed a decreased dry mass density with respect to leukocytes: 0.065 ± 0.006 pg/fL (HD-CTC) compared to 0.085 ± 0.004 pg/fL (leukocyte), p < 0.006. Quantification of HD-CTC dry mass content and volume provide key insights into the fluid dynamics of cancer, and may provide the rationale for strategies to isolate, monitor or target CTCs based on their physical properties. The parameters reported here can also be incorporated into blood cell flow models to better understand metastasis.

Original languageEnglish (US)
Article numberArticle 72
JournalFrontiers in Oncology
Volume2 JUL
DOIs
StatePublished - 2012

Keywords

  • Cellular density
  • Cellular mass
  • Cellular volume
  • Circulating tumor cell
  • Differential interference contrast
  • Ovarian cancer
  • Quantitative phase microscopy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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