The Human Melanoma Side Population Displays Molecular and Functional Characteristics of Enriched Chemoresistance and Tumorigenesis

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Wouters, Jasper ^a,b   Stas, Marguerite ^b   Gremeaux, Lies ^b   Govaere, Olivier ^a   Van den broeck, Anke ^b   Maes, Hannelore ^c   Agostinis, Patrizia ^c   Roskams, Tania ^a   van den Oord, Joost J ^a   Vankelecom, Hugo ^b  

^a DEPARTMENT OF IMAGING AND PATHOLOGY   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c LABORATORY OF MOLECULAR AND CELLULAR SIGNALING   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

DACARBAZINE; MULTIDRUG RESISTANCE PROTEIN 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER STEM CELL; CARCINOGENESIS; CELL COMPOSITION; CELL COUNT; CELL HYPOXIA; CELL INVASION; CELL MIGRATION; CELL SIZE; CLONOGENESIS; CONTROLLED STUDY; DISEASE CLASSIFICATION; GENE EXPRESSION; GENETIC ANALYSIS; HUMAN; HUMAN CELL; IMMUNOREACTIVITY; MALE; MELANOMA; MELANOMA CELL; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; SIDE POPULATION CELL; THERAPY RESISTANCE; UPREGULATION;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; DACARBAZINE; DISEASE PROGRESSION; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; JUMONJI DOMAIN-CONTAINING HISTONE DEMETHYLASES; MALE; MELANOMA; MICE; MICE, SCID; NEOPLASM PROTEINS; NEOPLASM STAGING; NEOPLASM TRANSPLANTATION; NEOPLASTIC STEM CELLS; NUCLEAR PROTEINS; P-GLYCOPROTEIN; REPRESSOR PROTEINS; SIDE-POPULATION CELLS; SKIN NEOPLASMS; TUMOR BURDEN;

EID: 84884846749     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0076550     Document Type: Article

References (79)

1. ACS (2012) Cancer Facts and Figures 2012. American Cancer Society.
2. Fukunaga-Kalabis M, Herlyn M, (2012) Beyond ABC: another mechanism of drug resistance in melanoma side population. J Invest Dermatol 132: 2317-2319. doi:10.1038/jid.2012.220. PubMed: 22971921.
3. Wu C, Alman BA, (2008) Side population cells in human cancers. Cancer Lett 268: 1-9. doi:10.1016/j.canlet.2008.03.048. PubMed: 18487012.
4. Girouard SD, Murphy GF, (2011) Melanoma stem cells: not rare, but well done. Lab Invest 91: 647-664. doi:10.1038/labinvest.2011.50. PubMed: 21445060.
5. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC, (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183: 1797-1806. doi:10.1084/jem.183.4.1797. PubMed: 8666936.
6. Wouters J, Stas M, Govaere O, Van den Eynde K, Vankelecom H, et al. (2012) Gene expression changes in melanoma metastases in response to high-dose chemotherapy during isolated limb perfusion. Pigment Cell. Melanoma Res 25: 454-465.
7. Monzani E, Facchetti F, Galmozzi E, Corsini E, Benetti A, et al. (2007) Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer 43: 935-946. doi:10.1016/j.ejca.2007.01.017. PubMed: 17320377.
8. Keshet GI, Goldstein I, Itzhaki O, Cesarkas K, Shenhav L, et al. (2008) MDR1 expression identifies human melanoma stem cells. Biochem Biophys Res Commun 368: 930-936. doi:10.1016/j.bbrc.2008.02.022. PubMed: 18279661.
9. Depeille P, Cuq P, Passagne I, Evrard A, Vian L, (2005) Combined effects of GSTP1 and MRP1 in melanoma drug resistance. Br J Cancer 93: 216-223. doi:10.1038/sj.bjc.6602681. PubMed: 15999103.
10. Luo Y, Ellis LZ, Dallaglio K, Takeda M, Robinson WA, et al. (2012) Side Population Cells from Human Melanoma Tumors Reveal Diverse Mechanisms for Chemoresistance. J Invest Dermatol, 132: 2440-50. PubMed: 22622430.
11. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, et al. (2006) Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66: 9339-9344. doi:10.1158/0008-5472.CAN-06-3126. PubMed: 16990346.
12. Reya T, Morrison SJ, Clarke MF, Weissman IL, (2001) Stem cells, cancer, and cancer stem cells. Nature 414: 105-111. doi:10.1038/35102167. PubMed: 11689955.
13. Wouters J, Vankelecom H, van den Oord J, (2009) Cancer stem cells in cutaneous melanoma. Expert Rev Dermatol 4: 225-235. doi:10.1586/edm.09.17.
14. Chen J, Li Y, Yu TS, McKay RM, Burns DK, et al. (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488: 522-526. doi:10.1038/nature11287. PubMed: 22854781.
15. Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C, (2012) Defining the mode of tumour growth by clonal analysis. Nature 488: 527-530. doi:10.1038/nature11344. PubMed: 22854777.
16. Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, et al. (2012) Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337: 730-735. doi:10.1126/science.1224676. PubMed: 22855427.
17. Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, et al. (2011) Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 17: 1086-1093. doi:10.1038/nm.2415. PubMed: 21873988.
18. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, et al. (2008) Identification of cells initiating human melanomas. Nature 451: 345-349. doi:10.1038/nature06489. PubMed: 18202660.
19. Dou J, Wen P, Hu W, Li Y, Wu Y, et al. (2009) Identifying tumor stem-like cells in mouse melanoma cell lines by analyzing the characteristics of side population cells. Cell Biol Int 33: 807-815. doi:10.1016/j.cellbi.2009.05.003. PubMed: 19477285.
20. Fukunaga-Kalabis M, Martinez G, Nguyen TK, Kim D, Santiago-Walker A, et al. (2010) Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population. Oncogene 29: 6115-6124. doi:10.1038/onc.2010.350. PubMed: 20729912.
21. Grichnik JM, Burch JA, Schulteis RD, Shan S, Liu J, et al. (2006) Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol 126: 142-153. doi:10.1038/sj.jid.5700017. PubMed: 16417230.
22. Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, et al. (2010) A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 141: 583-594. doi:10.1016/j.cell.2010.04.020. PubMed: 20478252.
23. Jilaveanu LB, Aziz SA, Kluger HM, (2009) Chemotherapy and biologic therapies for melanoma: do they work? Clin Dermatol 27: 614-625. doi:10.1016/j.clindermatol.2008.09.020. PubMed: 19880049.
24. Breslow A, (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172: 902-908. doi:10.1097/00000658-197011000-00017. PubMed: 5477666.
25. Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, et al. (1973) In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 51: 1417-1423. PubMed: 4357758.
26. Wu C, Wei Q, Utomo V, Nadesan P, Whetstone H, et al. (2007) Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res 67: 8216-8222. doi:10.1158/0008-5472.CAN-07-0999. PubMed: 17804735.
27. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, et al. (2004) A distinct "side population" of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci U S A 101: 14228-14233. doi:10.1073/pnas.0400067101. PubMed: 15381773.
28. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, et al. (2005) Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res 65: 6207-6219. doi:10.1158/0008-5472.CAN-05-0592. PubMed: 16024622.
29. Grade M, Hörmann P, Becker S, Hummon AB, Wangsa D, et al. (2007) Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas. Cancer Res 67: 41-56. doi:10.1158/0008-5472.CAN-06-1514. PubMed: 17210682.
30. Lindgren D, Liedberg F, Andersson A, Chebil G, Gudjonsson S, et al. (2006) Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q. Oncogene 25: 2685-2696. doi:10.1038/sj.onc.1209249. PubMed: 16532037.
31. Engelmann K, Shen H, Finn OJ, (2008) MCF7 side population cells with characteristics of cancer stem/progenitor cells express the tumor antigen MUC1. Cancer Res 68: 2419-2426. doi:10.1158/0008-5472.CAN-07-2249. PubMed: 18381450.
32. Graham SM, Vass JK, Holyoake TL, Graham GJ, (2007) Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources. Stem Cells 25: 3111-3120. doi:10.1634/stemcells.2007-0250. PubMed: 17717066.
33. Winnepenninckx V, Lazar V, Michiels S, Dessen P, Stas M, et al. (2006) Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 98: 472-482. doi:10.1093/jnci/djj103. PubMed: 16595783.
34. Shibuya H, Kato Y, Saito M, Isobe T, Tsuboi R, et al. (2003) Induction of apoptosis and/or necrosis following exposure to antitumour agents in a melanoma cell line, probably through modulation of Bcl-2 family proteins. Melanoma Res 13: 457-464. doi:10.1097/00008390-200310000-00004. PubMed: 14512787.
35. Rausch V, Liu L, Apel A, Rettig T, Gladkich J, et al. (2012) Autophagy mediates survival of pancreatic tumour-initiating cells in a hypoxic microenvironment. J Pathol 227: 325-335. doi:10.1002/path.3994. PubMed: 22262369.
36. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T, (2005) Opinion: migrating cancer stem cells- an integrated concept of malignant tumour progression. Nat Rev Cancer 5: 744-749. doi:10.1038/nrc1694. PubMed: 16148886.
37. Heddleston JM, Li Z, McLendon RE, Hjelmeland AB, Rich JN, (2009) The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle 8: 3274-3284. doi:10.4161/cc.8.20.9701. PubMed: 19770585.
38. Klinger P, Schietke RE, Warnecke C, Swoboda B, Wiesener M, et al. (2011) Deletion of the oxygen-dependent degradation domain results in impaired transcriptional activity of hypoxia-inducible factors. Transcription 2: 269-275. doi:10.4161/trns.2.6.18619. PubMed: 22223045.
39. Shen GM, Zhang FL, Liu XL, Zhang JW, (2010) Hypoxia-inducible factor 1-mediated regulation of PPP1R3C promotes glycogen accumulation in human MCF-7 cells under hypoxia. FEBS Lett 584: 4366-4372. doi:10.1016/j.febslet.2010.09.040. PubMed: 20888814.
40. Chen MF, Lu MS, Lin PY, Chen PT, Chen WC, et al. (2012) The role of DNA methyltransferase 3b in esophageal squamous cell carcinoma. Cancer 118: 4074-4089. doi:10.1002/cncr.26736. PubMed: 22213175.
41. Linhart HG, Lin H, Yamada Y, Moran E, Steine EJ, et al. (2007) Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev 21: 3110-3122. doi:10.1101/gad.1594007. PubMed: 18056424.
42. Chen T, Ueda Y, Dodge JE, Wang Z, Li E, (2003) Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol Cell Biol 23: 5594-5605. doi:10.1128/MCB.23.16.5594-5605.2003. PubMed: 12897133.
43. Tadokoro Y, Ema H, Okano M, Li E, Nakauchi H, (2007) De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. J Exp Med 204: 715-722. doi:10.1084/jem.20060750. PubMed: 17420264.
44. Martins-Taylor K, Schroeder DI, LaSalle JM, Lalande M, Xu RH, (2012) Role of DNMT3B in the regulation of early neural and neural crest specifiers. Epigenetics 7: 71-82. doi:10.4161/epi.7.1.18750. PubMed: 22207353.
45. Li Z, Bao S, Wu Q, Wang H, Eyler C, et al. (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15: 501-513. doi:10.1016/j.ccr.2009.03.018. PubMed: 19477429.
46. Roberts AM, Watson IR, Evans AJ, Foster DA, Irwin MS, et al. (2009) Suppression of hypoxia-inducible factor 2alpha restores p53 activity via Hdm2 and reverses chemoresistance of renal carcinoma cells. Cancer Res 69: 9056-9064. doi:10.1158/0008-5472.CAN-09-1770. PubMed: 19920202.
47. Bangoura G, Liu ZS, Qian Q, Jiang CQ, Yang GF, et al. (2007) Prognostic significance of HIF-2alpha/EPAS1 expression in hepatocellular carcinoma. World J Gastroenterol 13: 3176-3182. PubMed: 17589895.
48. Giatromanolaki A, Sivridis E, Kouskoukis C, Gatter KC, Harris AL, et al. (2003) Hypoxia-inducible factors 1alpha and 2alpha are related to vascular endothelial growth factor expression and a poorer prognosis in nodular malignant melanomas of the skin. Melanoma Res 13: 493-501. doi:10.1097/00008390-200310000-00008. PubMed: 14512791.
49. Beck S, Jin X, Sohn YW, Kim JK, Kim SH, et al. (2011) Telomerase activity-independent function of TERT allows glioma cells to attain cancer stem cell characteristics by inducing EGFR expression. Mol Cells 31: 9-15. doi:10.1007/s10059-011-0008-8. PubMed: 21193962.
50. Paranjape AN, Mandal T, Mukherjee G, Kumar MV, Sengupta K, et al. (2012) Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties. Oncogene 31: 1896-1909. doi:10.1038/onc.2011.378. PubMed: 21874052.
51. Biroccio A, Amodei S, Benassi B, Scarsella M, Cianciulli A, et al. (2002) Reconstitution of hTERT restores tumorigenicity in melanoma-derived c-Myc low-expressing clones. Oncogene 21: 3011-3019. doi:10.1038/sj.onc.1205415. PubMed: 12082531.
52. Clevers H, (2011) The cancer stem cell: premises, promises and challenges. Nat Med 17: 313-319. PubMed: 21386835.
53. Molinari A, Stringaro A, Gentile M, Colone M, Toccacieli L, et al. (2005) Invasive properties of multidrug resistant human melanoma cells. Ital J Anat Embryol 110: 135-141. PubMed: 16101031.
54. Colone M, Calcabrini A, Toccacieli L, Bozzuto G, Stringaro A, et al. (2008) The multidrug transporter P-glycoprotein: a mediator of melanoma invasion? J Invest Dermatol 128: 957-971. doi:10.1038/sj.jid.5701082. PubMed: 17943188.
55. Walsh N, Kennedy S, Larkin AM, Tryfonopoulos D, Eustace AJ, et al. (2010) Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis. Br J Cancer 102: 1157-1162. doi:10.1038/sj.bjc.6605590. PubMed: 20234362.
56. Arancia G, Molinari A, Calcabrini A, Meschini S, Cianfriglia M, (2001) Intracellular P-glycoprotein in multidrug resistant tumor cells. Ital J Anat Embryol 106: 59-68. PubMed: 11729998.
57. Molinari A, Calcabrini A, Meschini S, Marra M, Stringaro A, et al. (2002) What is the relationship between P-glycoprotein and adhesion molecule expression in melanoma cells? Melanoma Res 12: 109-114. doi:10.1097/00008390-200204000-00002. PubMed: 11930106.
58. Molinari A, Calcabrini A, Meschini S, Stringaro A, Del Bufalo D, et al. (1998) Detection of P-glycoprotein in the Golgi apparatus of drug-untreated human melanoma cells. Int J Cancer 75: 885-893. doi:10.1002/(SICI)1097-0215(19980316)75:6. PubMed: 9506534.
59. Zabierowski SE, Herlyn M, (2008) Learning the ABCs of melanoma-initiating cells. Cancer Cell 13: 185-187. doi:10.1016/j.ccr.2008.02.015. PubMed: 18328422.
60. Boiko AD, Razorenova OV, van de Rijn M, Swetter SM, Johnson DL, et al. (2010) Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature 466: 133-137. doi:10.1038/nature09161. PubMed: 20596026.
61. Civenni G, Walter A, Kobert N, Mihic-Probst D, Zipser M, et al. (2011) Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth. Cancer Res 71: 3098-3109. doi:10.1158/0008-5472.CAN-10-3997. PubMed: 21393506.
62. Vásquez-Moctezuma I, Meraz-Ríos MA, Villanueva-López CG, Magaña M, Martínez-Macias R, et al. (2010) ATP-binding cassette transporter ABCB5 gene is expressed with variability in malignant melanoma. Actas Dermosifiliogr 101: 341-348. doi:10.1016/j.ad.2009.12.006. PubMed: 20487690.
63. Kim M, Koh YJ, Kim KE, Koh BI, Nam DH, et al. (2010) CXCR4 signaling regulates metastasis of chemoresistant melanoma cells by a lymphatic metastatic niche. Cancer Res 70: 10411-10421. doi:10.1158/0008-5472.CAN-10-2591. PubMed: 21056990.
64. Seong I, Min HJ, Lee JH, Yeo CY, Kang DM, et al. (2012) Sox10 controls migration of B16F10 melanoma cells through multiple regulatory target genes. PLOS ONE 7: e31477. doi:10.1371/journal.pone.0031477. PubMed: 22363655.
65. Murakami T, Toda S, Fujimoto M, Ohtsuki M, Byers HR, et al. (2001) Constitutive activation of Wnt/beta-catenin signaling pathway in migration-active melanoma cells: role of LEF-1 in melanoma with increased metastatic potential. Biochem Biophys Res Commun 288: 8-15. doi:10.1006/bbrc.2001.5719. PubMed: 11594745.
66. Milde-Langosch K, Bamberger AM, Rieck G, Grund D, Hemminger G, et al. (2005) Expression and prognostic relevance of activated extracellular-regulated kinases (ERK1/2) in breast cancer. Br J Cancer 92: 2206-2215. doi:10.1038/sj.bjc.6602655. PubMed: 15928662.
67. Chen J, Gremeaux L, Fu Q, Liekens D, Van Laere S, et al. (2009) Pituitary progenitor cells tracked down by side population dissection. Stem Cells 27: 1182-1195. doi:10.1002/stem.51. PubMed: 19418455.
68. Metelmann HR, Von Hoff DD, (1983) In vitro activation of dacarbazine (DTIC) for a human tumor cloning system. Int J Cell Cloning 1: 24-32. doi:10.1002/stem.5530010105. PubMed: 6674387.
69. Virág L, Kerékgyártó C, Fachet J, (1995) A simple, rapid and sensitive fluorimetric assay for the measurement of cell-mediated cytotoxicity. J Immunol Methods 185: 199-208. doi:10.1016/0022-1759(95)00115-Q. PubMed: 7561130.
70. Baugh LR, Hill AA, Brown EL, Hunter CP, (2001) Quantitative analysis of mRNA amplification by in vitro transcription. Nucleic Acids Res 29: E29. doi:10.1093/nar/29.1.29. PubMed: 11222780.
71. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102: 15545-15550. doi:10.1073/pnas.0506580102. PubMed: 16199517.
72. Marshall OJ, (2004) PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time PCR. Bioinformatics 20: 2471-2472. doi:10.1093/bioinformatics/bth254. PubMed: 15073005.
73. Schmittgen TD, Livak KJ, (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3: 1101-1108. doi:10.1038/nprot.2008.73. PubMed: 18546601.
74. Scheper RJ, Bulte JW, Brakkee JG, Quak JJ, van der Schoot E, et al. (1988) Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multi-drug-resistance. Int J Cancer 42: 389-394. doi:10.1002/ijc.2910420314. PubMed: 2458323.
75. Vander Borght S, Libbrecht L, Blokzijl H, Faber KN, Moshage H, et al. (2005) Diagnostic and pathogenetic implications of the expression of hepatic transporters in focal lesions occurring in normal liver. J Pathol 207: 471-482. doi:10.1002/path.1852. PubMed: 16161006.
76. Blokzijl H, Vander Borght S, Bok LI, Libbrecht L, Geuken M, et al. (2007) Decreased P-glycoprotein (P-gp/MDR1) expression in inflamed human intestinal epithelium is independent of PXR protein levels. Inflamm Bowel Dis 13: 710-720. doi:10.1002/ibd.20088. PubMed: 17262809.
77. Vander Borght S, Komuta M, Libbrecht L, Katoonizadeh A, Aerts R, et al. (2008) Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin. Liver Int 28: 1370-1380. doi:10.1111/j.1478-3231.2008.01889.x. PubMed: 19055643.
78. Hayami S, Yoshimatsu M, Veerakumarasivam A, Unoki M, Iwai Y, et al. (2010) Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway. Mol Cancer 9: 59. doi:10.1186/1476-4598-9-59. PubMed: 20226085.
79. Uhlén M, Björling E, Agaton C, Szigyarto CA, Amini B, et al. (2005) A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics 4: 1920-1932. doi:10.1074/mcp.M500279-MCP200. PubMed: 16127175.