Clonal dominance of CD133+ subset population as risk factor in tumor progression and disease recurrence of human cutaneous melanoma

Sharma,Bhuvnesh  K.; Manglik,V.; O'Connell,Michael; Weeraratna,Ashani; McCarron,Edward   C.; Broussard,Jennifer  N.; Divito,Kyle  A.; Simbulan-Rosenthal,Cynthia  M.; Rosenthal,Dean  S.; Zapas,John L.

doi:10.3892/ijo.2012.1590

November 2012 Volume 41 Issue 5

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November 2012 Volume 41 Issue 5

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Article Open Access

Clonal dominance of CD133+ subset population as risk factor in tumor progression and disease recurrence of human cutaneous melanoma

Authors:
- Bhuvnesh K. Sharma
- V. Manglik
- Michael O'Connell
- Ashani Weeraratna
- Edward C. McCarron
- Jennifer N. Broussard
- Kyle A. Divito
- Cynthia M. Simbulan-Rosenthal
- Dean S. Rosenthal
- John L. Zapas
View Affiliations / Copyright

Affiliations: Department of Surgical Oncology, The Maryland Melanoma Center, The Harry and Jeanette Weinberg Cancer Institute, Baltimore, MD, USA, Elizabeth City State University, Elizabeth City, NC, USA, Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA, Department of Pathology, MedStar Franklin Square Medical Center, Baltimore, MD, USA, Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, School of Medicine, Washington, DC, USA

Copyright: © Sharma et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 1570-1576
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Published online on: August 17, 2012

https://doi.org/10.3892/ijo.2012.1590
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Abstract

Chemotherapeutic refractoriness of advanced cutaneous melanoma may be linked with melanoma-initiating cells, also known as melanoma stem cells. This study aimed to determine relative risk of clonal dominance of the CD133+ phenotype in tissues from melanoma patients with different clinical outcomes that could be applied to early diagnosis, prognosis or disease monitoring. Significant overexpression of CD133 (p<0.02) was observed by immunohistochemical staining in tissues from patients with recurrent disease versus those without disease recurrence. Relative risk analysis between these two groups suggested that the patients with recurrence or metastatic lesion had a greater than 2-fold overexpression of CD133. In addition, immunodetectable CD133 corroborated with upregulation of CD133 RNA levels (14- to 30-fold) as assessed by quantitative real-time reverse transcription-PCR (qRT-PCR) comparison of melanoma cell lines derived from patients with poor clinical outcomes and short overall survival (<10 months), vs. those derived from patients with good clinical outcomes and longer overall survival (>24 months). Further, cells derived from patients, and MACS-sorted according to their CD133 status retained their CD133-positivity (>95%) or CD133-negativity (>95%) for more than 8 passages in culture. CD133+ cells could repopulate and form tumors (p<0.03) in athymic NCr-nu/nu mice within 8 weeks while no tumors were observed with CD133- phenotype (up to 200,000 cells). Taken together, the study demonstrates, for the first time, that there exists a clonal dominance of a CD133+ population within the hierarchy of cells in cutaneous tissues from patients that have undergone successive progressive stages of melanoma, from primary to metastatic lesions. CD133, thus, provides a predictive marker of disease as well as a potential therapeutic target of high-risk melanoma.

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1.	T ReyaSJ MorrisonMF ClarkeIL WeissmanStem cells, cancers, and cancer stem cellsNature414105111200110.1038/3510216711689955
2.	IM Al-HajMS WichaA Benito-HernandezSJ MorrisonMF ClarkeProspective identification of tumorigenic breast cancer cellsProc Natl Acad Sci USA10039833988200310.1073/pnas.0530291100
3.	SK SinghID ClarkeM TerasakiVE BonnC HawkinsJ SquireDB DirksIdentification of a cancer stem cell in human brain tumorsCancer Res6358215828200314522905
4.	GG WulfRY WangI KuehneD WeinderF MariniMK BrennerM AndreeffMA GoodellA leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemiaBlood9811661173200110.1182/blood.V98.4.116611493466
5.	T KondoT SetoguchT TagaPersistence of a small subpopulation of cancer stem like cells in the C6 glioma cell lineProc Natl Acad Sci USA101781786200410.1073/pnas.030761810014711994
6.	JM GrichnikJA BurchRD SchulteisS ShanJ LiuTL DarrowCE VervaertHF SeiglerMelanoma, a tumor based on a mutant stem cell?J Invest Dermatol126142153200610.1038/sj.jid.570001716417230
7.	D FangTK NguyenK LeishearR FinkoAN KulpS HotzPA van BelleX XuDE ElderM HerlynA tumorigenic subpopulation with stem cell properties in melanomasCancer Res6593289337200510.1158/0008-5472.CAN-05-134316230395
8.	SE ZabierowskiM HerlynMelanoma stem cells: the dark seed of melanomaJ Clin Oncol2628902894200810.1200/JCO.2007.15.546518539969
9.	WM KleinBP WuS ZhaoH WuAJP Klein-SzantoSR TahanIncreased expression of stem cell markers in malignant melanomaMod Pathol20102107200710.1038/modpathol.380072017143262
10.	BK SharmaV ManglikEG EliasImmunoexpression of melanoma stem cell markers in various stages of disease in human melanomaJ Surg Res163e11e15201010.1016/j.jss.2010.03.04320638684
11.	CY ParkD TsengIL WeismanCancer stem cells-directed therapies: recent data from laboratory and clinicMol Ther172219230200910.1038/mt.2008.254
12.	I WeissmanStem cell research: paths to cancer therapies and regenerative medicineJAMA29413591366200510.1001/jama.294.11.135916174694
13.	SV ShmelkovR St ChairD LydenAC133/CD133/ Prominin-1Int J Biochem Cell Biol37715719200510.1016/j.biocel.2004.08.01015694831
14.	T SchattonGF MurphyNY FrankK YamauraAM Wagga-GasserM GasserQ ZhanS JordanLM DuncanC WeishauptRC FuhlbriggeTS KupperMH SayeghMH FrankIdentification of cells initiating human melanomasNature451345349200810.1038/nature0648918202660
15.	GW SwartPC LunterJW KilsdonkActivated leukocyte cell adhesion molecule (ALCAM/CD166): signaling at the divide of melanoma cell clustering and cell migration?Cancer Metastasis Rev24223236200510.1007/s10555-005-1573-015986133
16.	VA FlorenesR HolmO MyklebostExpression of the neuroectodermal intermediate filament Nestin in human melanomasCancer Res5435435619948275467
17.	MM TomaykoCP ReynoldsDetermination of subcutaneous tumor size in athymic (nude) miceCancer Chemother Pharmacol24148154198910.1007/BF003002342544306
18.	DM EuhusC HuddMC La ReginaFE JohnsonTumor measurement in the nude mouseJ Surg Oncol31229234198610.1002/jso.29303104023724177
19.	IL BotchkinaRA RowehlDE RivadenneiraMS Karpeh JrH CrawfordA DufourJ JuY WangY LeyfmanGI BotchkinaPhenotypic subpopulations of metastatic colon cancer stem cells: genomic analysisCancer Genomics Proteomics61929200919451087
20.	V TirinoR CamerlingoR FrancoD MalangaA La RoccaG VigliettoG RoccoG PirozziThe role of CD133 in the identification and characterization of tumor-initiating cells in non-small cell lung cancerEur J Cardiothorac Surg36446453200910.1016/j.ejcts.2009.03.06319464919
21.	G BertoliniL RozP PeregoM TortoretoE FontanellaL GattiG PratesiA FabbriF AndrianiS TinelliE RozR CaseriniS Lo VulloT CameriniL MarianiD DeliaE CalabroU PastorinoG SozziHighly tumorigenic lung cancer CD133⁺ cells display stem-like features and are spared by cisplatin treatmentProc Natl Acad Sci USA1061628116286200919805294
22.	S BaoQ WuRE McLendonY HaoY ShiAB HjelmelandMW DewhirstDD BignerJN RichGlioma stem cells promote radioresistance by preferential activation of the DNA damage responseNature444756760200610.1038/nature0523617051156
23.	SH ChiouCC YuCY HuangSC LinCJ LiuTH TsaiSH ChouCS ChienHH KuJF LoPositive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinomaClin Cancer Res1440854095200810.1158/1078-0432.CCR-07-440418593985
24.	MF ClarkeJE DickPB DirksCJ EavesCH JamiesonDL JonesJ VisvaderIL WeismannGM WahlCancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cellsCancer Res6693399344200610.1158/0008-5472.CAN-06-3126
25.	E MonzaniF FacchettiE GalmozziE CorsiniA BenettiC CavazzinA GrittiA PiccininiD PorroM SantinamiG InverniciE ParatiG AlessandariCA La PortaMelanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potentialEur J Cancer43935946200710.1016/j.ejca.2007.01.01717320377
26.	G RappaO FodstadA LoricoThe stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanomaStem Cells2630083017200810.1634/stemcells.2008-060118802032

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Clonal dominance of CD133+ subset population as risk factor in tumor progression and disease recurrence of human cutaneous melanoma

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