Detection of Lipid-Rich Prostate Circulating Tumour Cells with Coherent Anti-Stokes Raman Scattering Microscopy

Ranjana Mitra,Oscar B Goodman,Olivia Chao,Thuc T Le,Yasuyo Urasaki

doi:10.1186/1471-2407-12-540

Abstract

BackgroundCirculating 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.MethodsCoherent 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.ResultsOne 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.ConclusionsIntracellular 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.

Highlights

Circulating tumour cells (CTC) are an important indicator of metastasis and associated with a poor prognosis
We report the detection of lipid-rich CTC in the peripheral blood of metastatic prostate cancer patients with coherent anti-Stokes Raman scattering (CARS) microscopy
Detection of CTC in metastatic prostate cancer patients In the peripheral blood of metastatic prostate cancer patients, we detected the present of Hoeschst 33342 +CD45-CK+ cells (Figure 1, upper row), which were absent in the peripheral blood of healthy volunteers

Summary

Introduction

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. Circulating tumour cells (CTC) are malignant cells shed into the bloodstream. These cells spread to distant sites where they initiate metastases, the primary cause of cancer-specific mortality [1]. Patients with metastatic cancers are more likely to have CTC detected in their blood [2]. CTC are an important indicator of metastasis and are associated with a poor prognosis [3]. Enumeration of CTC is routinely used to ascertain the prognosis and monitor response to cancer treatments [4]. CTC represent an instantaneous sampling of the tumour burden and hold the key to understanding the stages of cancer metastasis including

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Conclusion