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Endothelial Interleukin‐6 Defines the Tumorigenic Potential of Primary Human Cancer Stem Cells
dc.contributor.authorKrishnamurthy, Sudhaen_US
dc.contributor.authorWarner, Kristy A.en_US
dc.contributor.authorDong, Zhihongen_US
dc.contributor.authorImai, Atsushien_US
dc.contributor.authorNör, Carolinaen_US
dc.contributor.authorWard, Brent B.en_US
dc.contributor.authorHelman, Joseph I.en_US
dc.contributor.authorTaichman, Russell S.en_US
dc.contributor.authorBellile, Emily L.en_US
dc.contributor.authorMcCauley, Laurie K.en_US
dc.contributor.authorPolverini, Peter J.en_US
dc.contributor.authorPrince, Mark E.en_US
dc.contributor.authorWicha, Max S.en_US
dc.contributor.authorNör, Jacques E.en_US
dc.date.accessioned2014-11-04T16:35:46Z
dc.date.availableWITHHELD_13_MONTHSen_US
dc.date.available2014-11-04T16:35:46Z
dc.date.issued2014-11en_US
dc.identifier.citationKrishnamurthy, Sudha; Warner, Kristy A.; Dong, Zhihong; Imai, Atsushi; Nör, Carolina ; Ward, Brent B.; Helman, Joseph I.; Taichman, Russell S.; Bellile, Emily L.; McCauley, Laurie K.; Polverini, Peter J.; Prince, Mark E.; Wicha, Max S.; Nör, Jacques E. (2014). "Endothelial Interleukinâ 6 Defines the Tumorigenic Potential of Primary Human Cancer Stem Cells." STEM CELLS 32(11): 2845-2857.en_US
dc.identifier.issn1066-5099en_US
dc.identifier.issn1549-4918en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/109335
dc.description.abstractHead and neck squamous cell carcinomas (HNSCC) contain a small subpopulation of stem cells endowed with unique capacity to generate tumors. These cancer stem cells (CSC) are localized in perivascular niches and rely on crosstalk with endothelial cells for survival and self‐renewal, but the mechanisms involved are unknown. Here, we report that stromal interleukin (IL)−6 defines the tumorigenic capacity of CSC sorted from primary human HNSCC and transplanted into mice. In search for the cellular source of Interleukin‐6 (IL‐6), we observed a direct correlation between IL‐6 levels in tumor‐associated endothelial cells and the tumorigenicity of CSC. In vitro, endothelial cell‐IL‐6 enhanced orosphere formation, p‐STAT3 activation, survival, and self‐renewal of human CSC. Notably, a humanized anti‐IL‐6R antibody (tocilizumab) inhibited primary human CSC‐mediated tumor initiation. Collectively, these data demonstrate that endothelial cell‐secreted IL‐6 defines the tumorigenic potential of CSC, and suggest that HNSCC patients might benefit from therapeutic inhibition of IL‐6/IL‐6R signaling. S tem C ells 2014;32:2845–2857en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherSquamous Cell Carcinomaen_US
dc.subject.otherSurvivalen_US
dc.subject.otherPerivascular Nicheen_US
dc.subject.otherSelf‐Renewalen_US
dc.subject.otherAngiogenesisen_US
dc.titleEndothelial Interleukin‐6 Defines the Tumorigenic Potential of Primary Human Cancer Stem Cellsen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/109335/1/stem1793.pdf
dc.identifier.doi10.1002/stem.1793en_US
dc.identifier.sourceSTEM CELLSen_US
dc.identifier.citedreferenceKim EK, Lim S, Park JM, et al. Human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by AMP‐activated protein kinase. J Cell Physiol 2012; 227: 1680 – 1687.en_US
dc.identifier.citedreferenceSansone P, Storci G, Tavolari S, et al. IL‐6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 2007; 117: 3988 – 4002.en_US
dc.identifier.citedreferenceWang H, Lathia JD, Wu Q, et al. Targeting interleukin‐6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells 2009; 27: 2393 – 2404.en_US
dc.identifier.citedreferenceMarotta LL, Almendro V, Marusyk A, et al. The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24‐ stem cell‐like breast cancer cells in human tumors. J Clin Invest 2011; 121: 2723 – 2735.en_US
dc.identifier.citedreferenceMakó V, Czúcz, J, Weiszhár, Z, et al. Proinflammatory activation pattern of human umbilical vein endothelial cells induced by IL‐1β, TNF‐α, and LPS. Cytometry A 2010; 77: 962 – 970.en_US
dc.identifier.citedreferenceKrishnamurthy S, Nör JE. Orosphere assay: A method for propagation of head and neck cancer stem cells. Head Neck 2013; 35: 1015 – 1021.en_US
dc.identifier.citedreferenceNör JE, Peters MC, Christensen JB, et al. Engineering and characterization of functional human microvessels in immunodeficient mice. Lab Invest 2001: 81: 453 – 463.en_US
dc.identifier.citedreferenceShinriki S, Jono H, Ota K, et al. Humanized anti‐interleukin‐6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin Cancer Res 2009; 15: 5426 – 5434.en_US
dc.identifier.citedreferenceDai J, Lin D, Zhang J, et al. Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL‐6 in mice. J Clin Invest 2000; 106: 887 – 895.en_US
dc.identifier.citedreferenceKaneko T, Okiji T, Kaneko R, et al. Laser‐capture microdissection for factor VIII‐expressing endothelial cells in cancer tissues. Methods Mol Biol 2011; 755: 395 – 403.en_US
dc.identifier.citedreferenceNeumeister V, Agarwal S, Bordeaux J, et al. In situ identification of putative stem cells by multiplexing ALDH1, CD44 and cytokeratin identifies breast cancer patients with poor prognosis. Am J Pathol 2010; 176: 2131 – 2138.en_US
dc.identifier.citedreferenceBiddle A, Liang X, Gammon L, et al. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res 2011; 71: 5317 – 5326.en_US
dc.identifier.citedreferenceNiwa H, Burdon T, Chambers I, et al. Self‐renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev 1998; 12: 2048 – 2060.en_US
dc.identifier.citedreferenceMatthews JR, Sansom OJ, Clarke AR. Absolute requirement for STAT3 function in small‐intestine crypt stem cell survival. Cell Death Differ 2011; 18: 1934 – 1943.en_US
dc.identifier.citedreferenceGuryanova OA, Wu Q, Cheng L, et al. Nonreceptor tyrosine kinase BMX maintains self‐renewal and tumorigenic potential of glioblastoma stem cells by activating STAT3. Cancer Cell 2011; 19: 498 – 511.en_US
dc.identifier.citedreferenceLin HY, Tsai CC, Chen LL, et al. Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK. J Biomed Sci 2010; 17: 56.en_US
dc.identifier.citedreferenceForastiere AA. Chemotherapy in the treatment of locally advanced head and neck cancer. J Surg Oncol 2008; 97: 701 – 707.en_US
dc.identifier.citedreferenceSano D, Myers JN. Metastasis of squamous cell carcinoma of the oral tongue. Cancer Metastasis Rev 2007; 26: 645 – 662.en_US
dc.identifier.citedreferenceJemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69 – 90.en_US
dc.identifier.citedreferenceGilbert LA, Hemann MT. DNA‐damage‐mediated induction of a chemoresistant niche. Cell 2010; 143: 355 – 366.en_US
dc.identifier.citedreferenceFranses JW, Baker AB, Chitalia VC, et al. Stromal endothelial cells directly influence cancer progression. Sci Transl Med 2011; 3: 66ra5.en_US
dc.identifier.citedreferenceGómez‐Gaviro MV, Lovell‐Badge R, Fernández‐Avilés F, et al. The vascular stem cell niche. J Cardiovas Transl Res 2012; 5: 618 – 630.en_US
dc.identifier.citedreferenceMakó V, Czúcz J, Weiszhár Z, et al. Proinflammatory activation pattern of human umbilical vein endothelial cells induced by IL‐1β, TNF‐α, and LPS. Cytometry A 2010; 77: 962 – 970.en_US
dc.identifier.citedreferenceNeiva KG, Zhang Z, Miyazawa M, et al. Crosstalk initiated by endothelial cells enhances migration and inhibits anoikis of squamous cell carcinoma cells through STAT3/Akt/ERK signaling. Neoplasia 2009; 11: 583 – 593.en_US
dc.identifier.citedreferenceGinestier C, Liu S, Diebel ME, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 2010; 120: 485 – 497.en_US
dc.identifier.citedreferenceHwang WL, Yang MH, Tsai ML, et al. SNAIL regulates Interleukin‐8 expression, stem cell‐like activity, and tumorigenicity of human colorectal carcinoma cells. Gastroenterology 2011; 141: 279 – 291.en_US
dc.identifier.citedreferenceZhang Z, Dong Z, Lauxen IS, et al. Endothelial cell‐secreted EGF induces epithelial to mesenchymal transition and endows head and neck cancer cells with stem‐like phenotype. Cancer Res 2014; 74: 2869 – 2881.en_US
dc.identifier.citedreferenceSullivan NJ, Sasser AK, Axel AE, et al. Interleukin‐6 induces an epithelial‐mesenchymal transition phenotype in human breast cancer cells. Oncogene 2009; 28: 2940 – 2947.en_US
dc.identifier.citedreferenceTanaka T, Ogata A, Narazaki M. Tocilizumab for the treatment of rheumatoid arthritis. Expert Rev Clin Immunol 2010; 6: 843 – 854.en_US
dc.identifier.citedreferenceRossi JF, Négrier S, James ND, et al. A phase I/II study of siltuximab (CNTO 328), an anti‐interleukin‐6 monoclonal antibody, in metastatic renal cell cancer. Br J Cancer 2010; 103: 1154 – 1162.en_US
dc.identifier.citedreferenceVoorhees PM, Chen Q, Small GW, et al. Targeted inhibition of interleukin‐6 with CNTO 328 sensitizes pre‐clinical models of multiple myeloma to dexamethasone‐mediated cell death. Br J Haematol 2009; 145: 481 – 490.en_US
dc.identifier.citedreferenceNeiva KG, Warner KA, Campos MS, et al. Endothelial cell‐derived interleukin‐6 regulates tumor growth. BMC Cancer 2014; 14: 99.en_US
dc.identifier.citedreferencePrince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 2007; 104: 973 – 978.en_US
dc.identifier.citedreferenceHermann PC, Bhaskar S, Cioffi M, et al. Cancer stem cells in solid tumors. Semin Cancer Biol 2010; 20: 77 – 84.en_US
dc.identifier.citedreferenceAl‐Swiahb JN, Chen CH, Chuang HC, et al. Clinical, pathological and molecular determinants in squamous cell carcinoma of the oral cavity. Future Oncol 2010; 6: 837 – 850.en_US
dc.identifier.citedreferenceChen YC, Chang CJ, Hsu HS, et al. Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer‐derived ALDH1‐positive cells by knockdown of Bmi‐1. Oral Oncol 2010; 46: 158 – 165.en_US
dc.identifier.citedreferenceKakarala M, Wicha MS. Implications of the cancer stem‐cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 2008: 26: 2813 – 2820.en_US
dc.identifier.citedreferencePolyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9: 265 – 273.en_US
dc.identifier.citedreferenceLobo NA, Shimono Y, Qian D, et al. The biology of cancer stem cells. Annu Rev Cell Dev Biol 2007; 23: 675 – 699.en_US
dc.identifier.citedreferenceKrishnamurthy S, Dong Z, Vodopyanov D, et al. Endothelial cell‐initiated signaling promotes the survival and self‐renewal of cancer stem cells. Cancer Res 2010; 70: 9969 – 9978.en_US
dc.identifier.citedreferenceGhajar CM, Peinado H, Mori H, et al. The perivascular niche regulates breast tumour dormancy. Nat Cell Biol 2013; 15: 807 – 817.en_US
dc.identifier.citedreferenceParmar A, Marz S, Rushton S, et al. Stromal niche cells protect early leukemic FLT3‐ITD+ progenitor cells against First‐generation FLT3 Tyrosine kinase inhibitors. Cancer Res 2011; 71: 4696 – 4706.en_US
dc.identifier.citedreferenceShen Q, Goderie SK, Jin L, et al. Endothelial cells stimulate self‐renewal and expand neurogenesis of neural stem cells. Science 2004; 304: 1338 – 1340.en_US
dc.identifier.citedreferenceCalabrese C, Poppleton H, Kocak M, et al. A perivascular niche for brain tumor stem cells. Cancer Cell 2007; 11: 69 – 82.en_US
dc.identifier.citedreferenceBergers G, Hanahan D. Modes of resistance to anti‐angiogenic therapy. Nat Rev Cancer 2008; 8: 592 – 603.en_US
dc.identifier.citedreferenceKeunen O, Johansson M, Oudin A, et al. Anti‐VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci USA 2011; 108: 3749 – 3754.en_US
dc.identifier.citedreferencePaez‐Ribes M, Allen E, Hudock J, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009; 15: 220 – 231.en_US
dc.identifier.citedreferenceRiedel F, Zaiss I, Herzog D, et al. Serum levels of interleukin‐6 in patients with primary head and neck squamous cell carcinoma. Anticancer Res 2005; 25: 2761 – 2765.en_US
dc.identifier.citedreferenceDuffy SA, Taylor JM, Terrell JE, et al. Interleukin‐6 predicts recurrence and survival among head and neck cancer patients. Cancer 2008; 113: 750 – 757.en_US
dc.identifier.citedreferenceGrandis JR, Drenning SD, Zeng Q, et al. Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci USA 2000; 97: 4227 – 4232.en_US
dc.identifier.citedreferenceLeong PL, Andrews GA, Johnson DE, et al. Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proc Natl Acad Sci USA 2003; 100: 4138 – 4143.en_US
dc.identifier.citedreferenceChen YW, Chen KH, Huang PI, et al. Cucurbitacin I suppressed stem‐like property and enhanced radiation‐induced apoptosis in head and neck squamous carcinoma‐derived CD44(+)ALDH1(+)cells. Mol Cancer Ther 2010; 11: 2879 – 2892.en_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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