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BMC Cancer
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

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

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

Published in: BMC Cancer | Issue 1/2012

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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.
Appendix
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Literature
1.
Pantel K, Brakenhoff RH, Brandt B: Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008, 8 (5): 329-340. 10.1038/nrc2375.CrossRefPubMed
2.
Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, Reuben JM, Doyle GV, Allard WJ, Terstappen LW, et al: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004, 351 (8): 781-791. 10.1056/NEJMoa040766.CrossRefPubMed
3.
Goodman OB, Fink LM, Symanowski JT, Wong B, Grobaski B, Pomerantz D, Ma Y, Ward DC, Vogelzang NJ: Circulating tumor cells in patients with castration-resistant prostate cancer baseline values and correlation with prognostic factors. Cancer Epidemiol Biomarkers Prev. 2009, 18 (6): 1904-1913. 10.1158/1055-9965.EPI-08-1173.CrossRefPubMed
4.
Kaiser J: Medicine. Cancer's circulation problem. Science. 2010, 327 (5969): 1072-1074. 10.1126/science.327.5969.1072.CrossRefPubMed
5.
Fidler IJ: The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer. 2003, 3 (6): 453-458. 10.1038/nrc1098.CrossRefPubMed
6.
Yu M, Stott S, Toner M, Maheswaran S, Haber DA: Circulating tumor cells: approaches to isolation and characterization. J Cell Biol. 2011, 192 (3): 373-382. 10.1083/jcb.201010021.CrossRefPubMedPubMedCentral
7.
Riethdorf S, Fritsche H, Muller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Janicke F, et al: Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the Cell Search system. Clin Cancer Res. 2007, 13 (3): 920-928. 10.1158/1078-0432.CCR-06-1695.CrossRefPubMed
8.
Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, et al: Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007, 450 (7173): 1235-1239. 10.1038/nature06385.CrossRefPubMedPubMedCentral
9.
Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schutze K, Capron F, Franco D, Pazzagli M, Vekemans M, et al: Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol. 2000, 156 (1): 57-63. 10.1016/S0002-9440(10)64706-2.CrossRefPubMedPubMedCentral
10.
Gertler R, Rosenberg R, Fuehrer K, Dahm M, Nekarda H, Siewert JR: Detection of circulating tumor cells in blood using an optimized density gradient centrifugation. Recent Results Cancer Res. 2003, 162: 149-155. 10.1007/978-3-642-59349-9_13.CrossRefPubMed
11.
Mohamed H, Murray M, Turner JN, Caggana M: Isolation of tumor cells using size and deformation. J Chromatogr A. 2009, 1216 (47): 8289-8295. 10.1016/j.chroma.2009.05.036.CrossRefPubMed
12.
Tan SJ, Yobas L, Lee GY, Ong CN, Lim CT: Microdevice for the isolation and enumeration of cancer cells from blood. Biomed Microdevices. 2009, 11 (4): 883-892. 10.1007/s10544-009-9305-9.CrossRefPubMed
13.
Krivacic RT, Ladanyi A, Curry DN, Hsieh HB, Kuhn P, Bergsrud DE, Kepros JF, Barbera T, Ho MY, Chen LB, et al: A rare-cell detector for cancer. Proc Natl Acad Sci U S A. 2004, 101 (29): 10501-10504. 10.1073/pnas.0404036101.CrossRefPubMedPubMedCentral
14.
Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, et al: Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008, 14 (9): 985-990. 10.1038/nm.1789.CrossRefPubMed
15.
Barriere G, Riouallon A, Renaudie J, Tartary M, Rigaud M: Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis. BMC Cancer. 2012, 12: 114-10.1186/1471-2407-12-114.CrossRefPubMedPubMedCentral
16.
Andreopoulou E, Yang LY, Rangel KM, Reuben JM, Hsu L, Krishnamurthy S, Valero V, Fritsche HA, Cristofanilli M: Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect versus Veridex Cell Search system. Int J Cancer. 2012, 130 (7): 1590-1597. 10.1002/ijc.26111.CrossRefPubMed
17.
Went PT, Lugli A, Meier S, Bundi M, Mirlacher M, Sauter G, Dirnhofer S: Frequent EpCam protein expression in human carcinomas. Hum Pathol. 2004, 35 (1): 122-128. 10.1016/j.humpath.2003.08.026.CrossRefPubMed
18.
Sieuwerts AM, Kraan J, Bolt J, van der Spoel P, Elstrodt F, Schutte M, Martens JW, Gratama JW, Sleijfer S, Foekens JA: Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. J Natl Cancer Inst. 2009, 101 (1): 61-66.CrossRefPubMedPubMedCentral
19.
Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN, Gao H, Jackson SA, Giordano A, Hortobagyi GN, et al: Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy. Int J Cancer. 2012, 130 (4): 808-816. 10.1002/ijc.26037.CrossRefPubMed
20.
Marrinucci D, Bethel K, Bruce RH, Curry DN, Hsieh B, Humphrey M, Krivacic RT, Kroener J, Kroener L, Ladanyi A, et al: Case study of the morphologic variation of circulating tumor cells. Hum Pathol. 2007, 38 (3): 514-519. 10.1016/j.humpath.2006.08.027.CrossRefPubMed
21.
Zipfel WR, Williams RM, Christie R, Nikitin AY, Hyman BT, Webb WW: Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci U S A. 2003, 100 (12): 7075-7080. 10.1073/pnas.0832308100.CrossRefPubMedPubMedCentral
22.
Urasaki Y, Johlfs MG, Fiscus RR, Le TT: Imaging immune and metabolic cells of visceral adipose tissues with multimodal nonlinear optical microscopy. PLoS One. 2012, 7 (6): e38418-10.1371/journal.pone.0038418.CrossRefPubMedPubMedCentral
23.
Le TT, Rehrer CW, Huff TB, Nichols MB, Camarillo IG, Cheng JX: Nonlinear optical imaging to evaluate the impact of obesity on mammary gland and tumor stroma. Mol Imaging. 2007, 6 (3): 205-211.PubMedPubMedCentral
24.
Le TT, Huff TB, Cheng JX: Coherent anti-Stokes Raman scattering imaging of lipids in cancer metastasis. BMC Cancer. 2009, 9: 42-10.1186/1471-2407-9-42.CrossRefPubMedPubMedCentral
25.
Evans CL, Xie XS: Coherent Anti-Stokes Raman Scattering Microscopy: Chemically Selective Imaging for Biology and Medicine. Annu Rev Anal Chem. 2008, 1 (1): 883-909. 10.1146/annurev.anchem.1.031207.112754.CrossRef
26.
Fang C, Dean J, Smith JW: A novel variant of ileal bile acid binding protein is up-regulated through nuclear factor-kappaB activation in colorectal adenocarcinoma. Cancer Res. 2007, 67 (19): 9039-9046. 10.1158/0008-5472.CAN-06-3690.CrossRefPubMed
27.
Das R, Hammamieh R, Neill R, Melhem M, Jett M: Expression pattern of fatty acid-binding proteins in human normal and cancer prostate cells and tissues. Clin Cancer Res. 2001, 7 (6): 1706-1715.PubMed
28.
Hammamieh R, Chakraborty N, Barmada M, Das R, Jett M: Expression patterns of fatty acid binding proteins in breast cancer cells. J Exp Ther Oncol. 2005, 5 (2): 133-143.PubMed
29.
Goto Y, Matsuzaki Y, Kurihara S, Shimizu A, Okada T, Yamamoto K, Murata H, Takata M, Aburatani H, Hoon DS, et al: A new melanoma antigen fatty acid-binding protein 7, involved in proliferation and invasion, is a potential target for immunotherapy and molecular target therapy. Cancer Res. 2006, 66 (8): 4443-4449. 10.1158/0008-5472.CAN-05-2505.CrossRefPubMed
30.
Stump DD, Fan X, Berk PD: Oleic acid uptake and binding by rat adipocytes define dual pathways for cellular fatty acid uptake. J Lipid Res. 2001, 42 (4): 509-520.PubMed
31.
Bello D, Webber MM, Kleinman HK, Wartinger DD, Rhim JS: Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18. Carcinogenesis. 1997, 18 (6): 1215-1223. 10.1093/carcin/18.6.1215.CrossRefPubMed
32.
Hayward SW, Dahiya R, Cunha GR, Bartek J, Deshpande N, Narayan P: Establishment and characterization of an immortalized but non-transformed human prostate epithelial cell line: BPH-1. In Vitro Cell Dev Biol Anim. 1995, 31 (1): 14-24. 10.1007/BF02631333.CrossRefPubMed
33.
Wu HC, Hsieh JT, Gleave ME, Brown NM, Pathak S, Chung LW: Derivation of androgen-independent human LNCaP prostatic cancer cell sublines: role of bone stromal cells. Int J Cancer. 1994, 57 (3): 406-412. 10.1002/ijc.2910570319.CrossRefPubMed
34.
Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, Pathak S, von Eschenbach AC, Chung LW: Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res. 1994, 54 (10): 2577-2581.PubMed
35.
Listenberger LL, Han XL, Lewis SE, Cases S, Farese RV, Ory DS, Schaffer JE: Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A. 2003, 100 (6): 3077-3082. 10.1073/pnas.0630588100.CrossRefPubMedPubMedCentral
36.
Prieur X, Mok CY, Velagapudi VR, Nunez V, Fuentes L, Montaner D, Ishikawa K, Camacho A, Barbarroja N, O'Rahilly S, et al: Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes. 2011, 60 (3): 797-809. 10.2337/db10-0705.CrossRefPubMedPubMedCentral
37.
Le TT, Yue S, Cheng JX: Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy. J Lipid Res. 2010, 51 (11): 3091-3102. 10.1194/jlr.R008730.CrossRefPubMedPubMedCentral
38.
Picchio M, Messa C, Landoni C, Gianolli L, Sironi S, Brioschi M, Matarrese M, Matei DV, De Cobelli F, Del Maschio A, et al: Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol. 2003, 169 (4): 1337-1340. 10.1097/01.ju.0000056901.95996.43.CrossRefPubMed
39.
Bradley MO, Webb NL, Anthony FH, Devanesan P, Witman PA, Hemamalini S, Chander MC, Baker SD, He L, Horwitz SB, et al: Tumor targeting by covalent conjugation of a natural fatty acid to paclitaxel. Clin Cancer Res. 2001, 7 (10): 3229-3238.PubMed
40.
Jones RJ, Hawkins RE, Eatock MM, Ferry DR, Eskens FA, Wilke H, Evans TR: A phase II open-label study of DHA-paclitaxel (Taxoprexin) by 2-h intravenous infusion in previously untreated patients with locally advanced or metastatic gastric or oesophageal adenocarcinoma. Cancer Chemother Pharmacol. 2008, 61 (3): 435-441. 10.1007/s00280-007-0486-8.CrossRefPubMed
41.
Brueckner B, Rius M, Markelova MR, Fichtner I, Hals PA, Sandvold ML, Lyko F: Delivery of 5-azacytidine to human cancer cells by elaidic acid esterification increases therapeutic drug efficacy. Mol Cancer Ther. 2010, 9 (5): 1256-1264. 10.1158/1535-7163.MCT-09-1202.CrossRefPubMed
42.
Lee KC, Maturo C, Rodriguez R, Nguyen HL, Shorr R: Nanomedicine-nanoemulsion formulation improves safety and efficacy of the anti-cancer drug paclitaxel according to preclinical assessment. J Nanosci Nanotechnol. 2011, 11 (8): 6642-6656. 10.1166/jnn.2011.3928.CrossRefPubMed
43.
Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D, Weidhaas JB, Bader AG, Slack FJ: Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther. 2011, 19 (6): 1116-1122. 10.1038/mt.2011.48.CrossRefPubMedPubMedCentral
44.
Weeks T, Schie I, den Hartigh LJ, Rutledge JC, Huser T: Lipid-cell interactions in human monocytes investigated by doubly-resonant coherent anti-Stokes Raman scattering microscopy. J Biomed Opt. 2011, 16 (2): 021117-10.1117/1.3544585.CrossRefPubMedPubMedCentral
45.
den Hartigh LJ, Connolly-Rohrbach JE, Fore S, Huser TR, Rutledge JC: Fatty acids from very low-density lipoprotein lipolysis products induce lipid droplet accumulation in human monocytes. J Immunol. 2011, 184 (7): 3927-3936.CrossRef
46.
Bozza PT, Magalhaes KG, Weller PF: Leukocyte lipid bodies - Biogenesis and functions in inflammation. Biochim Biophys Acta. 2009, 1791 (6): 540-551. 10.1016/j.bbalip.2009.01.005.CrossRefPubMedPubMedCentral
47.
Wu H, Gower RM, Wang H, Perrard XY, Ma R, Bullard DC, Burns AR, Paul A, Smith CW, Simon SI, et al: Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation. 2009, 119 (20): 2708-2717. 10.1161/CIRCULATIONAHA.108.823740.CrossRefPubMedPubMedCentral
48.
49.
Gao L, Zhou H, Thrall MJ, Li F, Yang Y, Wang Z, Luo P, Wong KK, Palapattu GS, Wong ST: Label-free high-resolution imaging of prostate glands and cavernous nerves using coherent anti-Stokes Raman scattering microscopy. Biomed Opt Express. 2011, 2 (4): 915-926. 10.1364/BOE.2.000915.CrossRefPubMedPubMedCentral
50.
Yang Y, Li F, Gao L, Wang Z, Thrall MJ, Shen SS, Wong KK, Wong ST: Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging. Biomed Opt Express. 2011, 2 (8): 2160-2174. 10.1364/BOE.2.002160.CrossRefPubMedPubMedCentral
51.
Wyckoff J, Gligorijevic B, Entenberg D, Segall J, Condeelis J: High-resolution multiphoton imaging of tumors in vivo. Cold Spring Harb Protoc. 2011, 2011 (10): 1167-1184.PubMedPubMedCentral
52.
Brown EB, Campbell RB, Tsuzuki Y, Xu L, Carmeliet P, Fukumura D, Jain RK: In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy. Nat Med. 2001, 7 (7): 864-868. 10.1038/89997.CrossRefPubMed
53.
Chowdary PD, Jiang Z, Chaney EJ, Benalcazar WA, Marks DL, Gruebele M, Boppart SA: Molecular histopathology by spectrally reconstructed nonlinear interferometric vibrational imaging. Cancer Res. 2010, 70 (23): 9562-9569. 10.1158/0008-5472.CAN-10-1554.CrossRefPubMedPubMedCentral
54.
55.
Saar BG, Johnston RS, Freudiger CW, Xie XS, Seibel EJ: Coherent Raman scanning fiber endoscopy. Opt Lett. 2011, 36 (13): 2396-2398. 10.1364/OL.36.002396.CrossRefPubMedPubMedCentral
56.
Belanger E, Crepeau J, Laffray S, Vallee R, De Koninck Y, Te Co D: Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy. J Biomed Opt. 2012, 17 (2): 021107-10.1117/1.JBO.17.2.021107.CrossRefPubMed
57.
Konig K, Ehlers A, Riemann I, Schenkl S, Buckle R, Kaatz M: Clinical two-photon microendoscopy. Microsc Res Tech. 2007, 70 (5): 398-402. 10.1002/jemt.20445.CrossRefPubMed
58.
Wang HW, Chai N, Wang P, Hu S, Dou W, Umulis D, Wang LV, Sturek M, Lucht R, Cheng JX: Label-free bond-selective imaging by listening to vibrationally excited molecules. Phys Rev Lett. 2011, 106 (23): 238106-CrossRefPubMedPubMedCentral
59.
Georgakoudi I, Solban N, Novak J, Rice WL, Wei X, Hasan T, Lin CP: In vivo flow cytometry: a new method for enumerating circulating cancer cells. Cancer Res. 2004, 64 (15): 5044-5047. 10.1158/0008-5472.CAN-04-1058.CrossRefPubMed
60.
He W, Wang HF, Hartmann LC, Cheng JX, Low PS: In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry. Proc Natl Acad Sci U S A. 2007, 104 (28): 11760-11765. 10.1073/pnas.0703875104.CrossRefPubMedPubMedCentral
Metadata
Title
Detection of Lipid-Rich Prostate Circulating Tumour Cells with Coherent Anti-Stokes Raman Scattering Microscopy
Authors
Ranjana Mitra
Olivia Chao
Yasuyo Urasaki
Oscar B Goodman
Thuc T Le
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-540

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