Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts

Laboratory Investigation

Volumn 92, Issue 7, 2012, Pages 952-966

  Martin Padura, Ines ^a   Marighetti, Paola ^a   Agliano, Alice ^a,b   Colombo, Federico ^c   Larzabal, Leyre ^b   Redrado, Miriam ^b   Bleau, Anne Marie ^b   Prior, Celia ^b   Bertolini, Francesco ^a   Calvo, Alfonso ^b  

^a EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

^b UNIVERSITY OF NAVARRA   (Spain)

^c FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

Author keywords

angiogenesis; cancer stem cells; hepatocellular carcinoma; metronomic chemotherapy; NSG; xenograft

Indexed keywords

ALPHA FETOPROTEIN; BESTATIN; CYCLINE; CYCLOPHOSPHAMIDE; LUCIFERASE; MICROSOMAL AMINOPEPTIDASE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY G6.31; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIANGIOGENIC ACTIVITY; ANTIANGIOGENIC THERAPY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER CELL; CANCER REGRESSION; CANCER STEM CELL; CELL GROWTH; CELL STRUCTURE; CONTROLLED STUDY; DRUG POTENTIATION; DRUG TARGETING; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; LIVER CELL CARCINOMA; LIVER METASTASIS; LIVER PARENCHYMA; MALE; METRONOMIC DRUG ADMINISTRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; TUMOR RECURRENCE; TUMOR VOLUME;

ADMINISTRATION, METRONOMIC; ANGIOGENESIS INHIBITORS; ANIMALS; ANTIGENS, CD13; ANTINEOPLASTIC AGENTS, ALKYLATING; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL LINE, TUMOR; CYCLOPHOSPHAMIDE; DRUG SYNERGISM; HUMANS; LEUCINE; LIVER NEOPLASMS, EXPERIMENTAL; MALE; MICE; MICE, INBRED NOD; MICE, KNOCKOUT; MICE, SCID; NEOPLASM, RESIDUAL; NEOPLASTIC STEM CELLS; SPHEROIDS, CELLULAR; VASCULAR ENDOTHELIAL GROWTH FACTOR A; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84862980672     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2012.65     Document Type: Article

References (45)

1. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907-1917. (Pubitemid 37518510)
2. Voiculescu M, Winkler RE, Moscovici M, et al. Chemotherapies and targeted therapies in advanced hepatocellular carcinoma: from laboratory to clinic. J Gastrointestin Liver Dis 2008;17:315-322.
3. Hoshida Y, Villanueva A, Kobayashi M, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 2008;359:1995-2004.
4. Hanahan D, Bergers G, Bergsland E. Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 2000;105:1045-1047. (Pubitemid 30217688)
5. Bertolini F, Paul S, Mancuso P, et al. Maximum tolerable dose and lowdose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 2003;63:4342-4346. (Pubitemid 36951001)
6. Man S, Bocci G, Francia G, et al. Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res 2002;62:2731-2735. (Pubitemid 34525751)
7. Scripture CD, Sparreboom A, Figg WD. Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol 2005;6:780-789. (Pubitemid 41430719)
8. Pasquier E, Kavallaris M, Andre N. Metronomic chemotherapy: new rationale for new directions. Nat Rev Clin Oncol 2010;7:455-465.
9. Coghlin C, Murray GI. Current and emerging concepts in tumour metastasis. J Pathol 2010;222:1-15.
10. Yao Z, Mishra L. Cancer stem cells and hepatocellular carcinoma. Cancer Biol Ther 2009;8:1691-1698.
11. Morrison SJ, Kimble J. Asymmetric and symmetric stem-cell divisions in development and cancer. Nature 2006;441:1068-1074. (Pubitemid 43990718)
12. Morrison SJ, Spradling AC. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 2008;132: 598-611. (Pubitemid 351253690)
13. Haraguchi N, Utsunomiya T, Inoue H, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells 2006;24:506-513. (Pubitemid 44464754)
14. Zhu Z, Hao X, Yan M, et al. Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer 2010;126:2067-2078.
15. Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 2008;13:153-166. (Pubitemid 351163165)
16. Haraguchi N, Ishii H, Mimori K, et al. CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest 2010;120:3326-3339.
17. Yamashita T, Ji J, Budhu A, et al. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 2009;136:1012-1024.
18. Folkins C, Man S, Xu P, et al. Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res 2007; 67:3560-3564. (Pubitemid 46762138)
19. Colombo F, Baldan F, Mazzucchelli S, et al. Evidence of distinct tumourinitiating cells with different properties in primary human hepatocellular carcinoma. PLoS One 2011; 6:e21369.
20. Cicalese A, Bonizzi G, Pasi CE, et al. The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 2009;138:1083-1095.
21. Liang WC, Wu X, Peale FV, et al. Cross-species vascular endothelial growth factor (VEGF)-blocking antibodies completely inhibit the growth of human tumor xenografts and measure the contribution of stromal VEGF. J Biol Chem 2006;281:951-961.
22. Mancuso P, Antoniotti P, Quarna J, et al. Validation of a standardized method for enumerating circulating endothelial cells and progenitors: flow cytometry and molecular and ultrastructural analyses. Clin Cancer Res 2009;15:267-273.
23. Martin-Padura I, Agliano A, Marighetti P, et al. Sex-related efficiency in NSG mouse engraftment. Blood 2010;116:2616-2617.
24. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010;29: 4741-4751.
25. Manzotti C, Audisio RA, Pratesi G. Importance of orthotopic implantation for human tumors as model systems: relevance to metastasis and invasion. Clin Exp Metastasis 1993;11:5-14. (Pubitemid 23045685)
26. Tang TC, Man S, Lee CR, et al. Impact of metronomic UFT/cyclophosphamide chemotherapy and antiangiogenic drug assessed in a new preclinical model of locally advanced orthotopic hepatocellular carcinoma. Neoplasia 2010;12:264-274.
27. Shao YY, Lin ZZ, Hsu C, et al. Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma. Cancer 2010;116:4590-4596.
28. Ng IO, Poon RT, Lee JM, et al. Microvessel density, vascular endothelial growth factor and its receptors Flt-1 and Flk-1/KDR in hepatocellular carcinoma. Am J Clin Pathol 2001;116:838-845. (Pubitemid 33108154)
29. Moon WS, Rhyu KH, Kang MJ, et al. Overexpression of VEGF and angiopoietin 2: a key to high vascularity of hepatocellular carcinoma? Mod Pathol 2003;16:552-557. (Pubitemid 36718436)
30. Poon RT, Lau C, Pang R, et al. High serum vascular endothelial growth factor levels predict poor prognosis after radiofrequency ablation of hepatocellular carcinoma: importance of tumor biomarker in ablative therapies. Ann Surg Oncol 2007;14:1835-1845. (Pubitemid 46870942)
31. Poon RT, Ho JW, Tong CS, et al. Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. Br J Surg 2004;91:1354-1360. (Pubitemid 39331462)
32. Chiang DY, Villanueva A, Hoshida Y, et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res 2008;68:6779-6788.
33. Siegel AB, Olsen SK, Magun A, et al. Sorafenib: where do we go from here? Hepatology 2010;52:360-369.
34. Kerbel RS, Kamen BA. The anti-angiogenic basis of metronomic chemotherapy. Nat Rev Cancer 2004;4:423-436. (Pubitemid 38745528)
35. Molloy TJ, Bosma AJ, Baumbusch LO, et al. The prognostic significance of tumor cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res 2011;13:R61.
36. Xu W, Cao L, Chen L, et al. Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res 2011;17:3783-3793.
37. Aguirre-Ghiso JA. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 2007;7:834-846. (Pubitemid 350006258)
38. van Zijl F, Mikulits W. Hepatospheres: three dimensional cell cultures resemble physiological conditions of the liver. World J Hepatol 2010;2:1-7.
39. Liu LL, Fu D, Ma Y, et al. The power and the promise of liver cancer stem cell markers. Stem Cells Dev 2011;20:2023-2030.
40. Wang XQ, Ongkeko WM, Chen L, et al. Octamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4-AKT-ATP-binding cassette G2 pathway. Hepatology 2010;52:528-539.
41. Zeng Q, Yang Z, Gao YJ, et al. Treating triple-negative breast cancer by a combination of rapamycin and cyclophosphamide: an in vivo bioluminescence imaging study. Eur J Cancer 2010;46:1132-1143.
42. Zielske SP, Spalding AC, Lawrence TS. Loss of tumor-initiating cell activity in cyclophosphamide-treated breast xenografts. Transl Oncol 2010;3:149-152.
43. Bauvois B, Dauzonne D. Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects. Med Res Rev 2006;26:88-130. (Pubitemid 43986471)
44. Inagaki Y, Tang W, Zhang L, et al. Novel aminopeptidase N (APN/CD13) inhibitor 24F can suppress invasion of hepatocellular carcinoma cells as well as angiogenesis. Biosci Trends 2010;4:56-60.
45. Haraguchi N, Ishii H, Mimori K, et al. CD13 is a therapeutic target in human liver cancer stem cells. J Clin Invest 2010;120:3326-3339.