C-Terminal-PEDF Reduces IC50 Doses and Chemoresistant Population of CD133 and BCRP1-Positve Cancer Stem Like Cells

Authors

  • Paola Castro-Garcia Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain
  • Carmen Gil-Gas Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain
  • Paloma Honrubia-Gómez Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain
  • Carmen Belen Alvarez-Simón Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain
  • Jesús-José Ferré-Fernández Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain
  • Francisco Sánchez-Sánchez Genetic Area, Medicine Faculty/IDINE, University of Castilla-La Mancha, Spain
  • Jose Luis Sánchez-Sánchez Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain; Oncology Unit, University Hospital Complex of Albacete (CHUA), Spain
  • Jose Mª Garcia-Bueno Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain; Oncology Unit, University Hospital Complex of Albacete (CHUA), Spain
  • Sebastiá Sabater Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain: Radioterapy Unit, University Hospital Complex of Albacete (CHUA), Spain
  • Guadalupe Aparicio Medical Oncology Department, A Coruña University Hospital, Spain
  • Luis Miguel Antón-Aparicio Medical Oncology Department, A Coruña University Hospital, Spain
  • Carmen Ramírez-Castillejo Cancer Stem Cells laboratory, Regional Centre of Biomedical Research, University of Castilla- La Mancha, Spain

DOI:

https://doi.org/10.6000/1927-7229.2013.02.04.2

Keywords:

BCRP1, ABCG2, ABC transporter family, EpCAM, DFFDA, long retaining labelling cells, Cancer stem cell, self renewal inhibition, asymmetric division, Pigmented epithelium derived factor (PEDF)

Abstract

We report on two patients, successfully treated by the combination therapy of gemcitabine and 24-h intravenous infusion of cisplatin, who were initially diagnosed with node-positive advanced urothelial cancer. Each patient had a very good clinical response and underwent curative radical surgery after gemcitabine/cisplatin chemotherapy. A microscopically detailed examination of surgically obtained specimens showed the complete disappearance of malignant cells in the two cases. As a pilot study, we have used the regimen of gemcitabine plus 24-h continuous infusion of cisplatin, instead of bolus injection, for the treatment of 20 patients with node-positive or metastatic urothelial cancer. The clinical response rate in this regimen was 75% (complete response 7/20; 35%, partial response 8/20; 40%). The median overall survival was 665 days. As for the adverse effects, the incidences of severe neutropenia and thrombocytopenia (grade 3-4) were 20% and 15%, which might be less toxic than conventional gemcitabine plus cisplatin therapy. The 24-h infusion of cisplatin combined with gemcitabine can be highly recommended as neoadjuvant chemotherapy for locally advanced urothelial cancer.

References

Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-11. http://dx.doi.org/10.1038/35102167

Bapat SA. Evolution of cancer stem cells. Semin Cancer Biol 2007; 17: 204-13. http://dx.doi.org/10.1016/j.semcancer.2006.05.001

Balch C, Nephew KP, Huang TH, Bapat SA. Epigenetic ""bivalently marked"" process of cancer stem cell-driven tumorigenesis. Bioessays 2007; 29: 842-45. http://dx.doi.org/10.1002/bies.20619

Miller SJ, Lavker RM, Sun TT. Interpreting epithelial cancer biology in the context of stem cells: tumor properties and therapeutic implications. Biochim Biophys Acta 2005; 1756: 25-52.

Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol 2007; 23: 675-99. http://dx.doi.org/10.1146/annurev.cellbio.22.010305.104154

Sakariassen PO, Immervoll H, Chekenya M. Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia 2007; 9: 882-92. http://dx.doi.org/10.1593/neo.07658

Glinsky GV, Berezovska O, Glinskii AB. Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 2005; 115: 1503-21. http://dx.doi.org/10.1172/JCI23412

Galderisi U, Cipollaro M, Giordano A. Stem cells and brain cancer. Cell Death Differ 2006; 13: 5-11. http://dx.doi.org/10.1038/sj.cdd.4401757

Tu LC, Foltz G, Lin E, Hood L, Tian Q. Targeting stem cells-clinical implications for cancer therapy. Curr Stem Cell Res Ther 2009; 4: 147-53. http://dx.doi.org/10.2174/157488809788167373

Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA 2004; 101: 781-86. http://dx.doi.org/10.1073/pnas.0307618100

Kondo T. Stem cell-like cancer cells in cancer cell lines. Cancer Biomarkers 2007; 3: 245-50.

Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005; 434: 843-50. http://dx.doi.org/10.1038/nature03319

Cogan N, et al. DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase. Mutat Res 2009.

Nakeff A, Sahay N, Pisano M, Subramanian B. Painting with a molecular brush: genomic/proteomic interfacing to define the drug action profile of novel solid-tumor selective anticancer agents. Cytometry 2002; 47: 72-79. http://dx.doi.org/10.1002/cyto.10038

Beier D, et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth charac-terristics and molecular profiles. Cancer Res 2007; 67: 4010-15. http://dx.doi.org/10.1158/0008-5472.CAN-06-4180

Bjerkvig R, Tysnes BB, Aboody KS, Najbauer J, Terzis AJ. Opinion: the origin of the cancer stem cell: current controversies and new insights. Nat Rev Cancer 2005; 5: 899-904. http://dx.doi.org/10.1038/nrc1740

Singh SK, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63: 5821-28.

Liu G, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 2006; 5: 67. http://dx.doi.org/10.1186/1476-4598-5-67

Zhou L, Wei X, Cheng L, Tian J, Jiang JJ. CD133, one of the markers of cancer stem cells in Hep-2 cell line. Laryngoscope 2007; 117: 455-60. http://dx.doi.org/10.1097/01.mlg.0000251586.15299.35

Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3: 730-37. http://dx.doi.org/10.1038/nm0797-730

Garcia Bueno JM, et al. An update on the biology of cancer stem cells in breast cancer. Clin Transl Oncol 2008; 10: 786-93. http://dx.doi.org/10.1007/s12094-008-0291-9

Burns JS, et al. Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells. Cancer Res 2005; 65: 3126-35.

Sakariassen PO, Immervoll H, Chekenya M. Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia 2007; 9: 882-92. http://dx.doi.org/10.1593/neo.07658

Garcia Bueno JM, et al. An update on the biology of cancer stem cells in breast cancer. Clin Transl Oncol 2008; 10: 786-93. http://dx.doi.org/10.1007/s12094-008-0291-9

Barnstable CJ, Tombran-Tink J. Neuroprotective and antiangiogenic actions of PEDF in the eye: molecular targets and therapeutic potential. Prog Retin Eye Res 2004; 23: 561-77. http://dx.doi.org/10.1016/j.preteyeres.2004.05.002

Palmer TD, Takahashi J, Gage FH. The adult rat hippocampus contains primordial neural stem cells. Mol Cell Neurosci 1997; 8: 389-404. http://dx.doi.org/10.1006/mcne.1996.0595

Notari L, et al. Identification of a lipase-linked cell-membrane receptor for Pigment Epithelium-derived factor (PEDF). J Biol Chem 2006; 281: 38022-37. http://dx.doi.org/10.1074/jbc.M600353200

Bernard A, et al. Laminin receptor involvement in the anti-angiogenic activity of pigment epithelium-derived factor. J Biol Chem 2009; 284: 10480-490. http://dx.doi.org/10.1074/jbc.M809259200

Benda P, Lightbody J, Sato G, Levine L, Sweet W. Differentiated rat glial cell strain in tissue culture. Science 1968; 161: 371. http://dx.doi.org/10.1126/science.161.3839.370

Ferron S, et al. Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development 2004; 131: 4059-70. http://dx.doi.org/10.1242/dev.01215

Baba T, et al. Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene 2009; 28: 209-18. http://dx.doi.org/10.1038/onc.2008.374

Ramirez-Castillejo C, et al. Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 2006; 9: 331-39. http://dx.doi.org/10.1038/nn1657

Niño de Guzmán Méndez J, Barrientos Pelaez C. Neurocirugía. Universidad Nacional Mayor de San Marcos (Lima). Facultad de Medicina. Escuela Académico Profesional de Medicina Humana. Departamento Académico de Cirugía (ed.) 2002.

Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med 2007; 58: 267-84. http://dx.doi.org/10.1146/annurev.med.58.062105.204854

Clarke MF, Fuller M. Stem cells and cancer: two faces of eve. Cell 2006; 124: 1111-15. http://dx.doi.org/10.1016/j.cell.2006.03.011

Mao Q, Unadkat JD. Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J 2005; 7: E118-E133.

Clark MA, Perks CM, Winters ZE, Holly JM. DNA damage uncouples the mitogenic response to IGF-I in MCF-7 malignant breast cancer cells by switching the roles of PI3 kinase and p21WAF1/Cip1. Int J Cancer 2005; 116: 506-13. http://dx.doi.org/10.1002/ijc.21029

Monzo M, Navarro A, Ferrer G, Artells R. Pharmaco-genomics: a tool for improving cancer chemotherapy. Clin Transl Oncol 2008; 10: 628-37. http://dx.doi.org/10.1007/s12094-008-0263-0

Dittmar T, Heyder C, Gloria-Maercker E, Hatzmann W, Zanker KS. Adhesion molecules and chemokines: the navigation system for circulating tumor (stem) cells to metastasize in an organ-specific manner. Clin Exp Metastasis 2008; 25: 11-32. http://dx.doi.org/10.1007/s10585-007-9095-5

Sieuwerts AM. et al. Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. J Natl Cancer Inst 2009; 101: 61-66. http://dx.doi.org/10.1093/jnci/djn419

Bidlingmaier S, Zhu X, Liu B. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells. J Mol Med 2008; 86: 1025-32. http://dx.doi.org/10.1007/s00109-008-0357-8

Corbeil D, et al. The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 2000; 275: 5512-20. http://dx.doi.org/10.1074/jbc.275.8.5512

Pumiglia K, Temple S. PEDF: bridging neurovascular interactions in the stem cell niche. Nat Neurosci 2006; 9: 299-300. http://dx.doi.org/10.1038/nn0306-299

Maik-Rachline G, Shaltiel S, Seger R. Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor. Blood 2005; 105: 670-78. http://dx.doi.org/10.1182/blood-2004-04-1569

Maik-Rachline G, Seger R. Variable phosphorylation states of pigment-epithelium-derived factor differentially regulate its function. Blood 2006; 107: 2745-52. http://dx.doi.org/10.1182/blood-2005-06-2547

Andreu-Agullo C, Morante-Redolat JM, Delgado AC, Farinas I. Vascular niche factor PEDF modulates Notch-dependent stemness in the adult subependymal zone. Nat Neurosci 2009. http://dx.doi.org/10.1038/nn.2437

Lapidot T, et al. Identification of human juvenile chronic myelogenous leukemia stem cells capable of initiating the disease in primary and secondary SCID mice. Blood 1996; 88: 2655-64.

Singh SK, et al. Identification of human brain tumour initiating cells. Nature 2004; 432: 396-401. http://dx.doi.org/10.1038/nature03128

Fang D, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 2005; 65: 9328-37. http://dx.doi.org/10.1158/0008-5472.CAN-05-1343

Al Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100: 3983-88. http://dx.doi.org/10.1073/pnas.0530291100

Rizzo S, Attard G, Hudson DL. Prostate epithelial stem cells. Cell Prolif 2005; 38: 363-74. http://dx.doi.org/10.1111/j.1365-2184.2005.00356.x

Rausch V, et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell charac-terristics. Cancer Res 2010; 70: 5004-13. http://dx.doi.org/10.1158/0008-5472.CAN-10-0066

Tao H, Zhu Y. Colorectal cancer stem cell: a potential therapeutic target. Clin Transl Oncol 2011; 13: 833-38. http://dx.doi.org/10.1007/s12094-011-0743-5

Prince ME, 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: 973-78. http://dx.doi.org/10.1073/pnas.0610117104

Published

2013-12-28

How to Cite

Paola Castro-Garcia, Carmen Gil-Gas, Paloma Honrubia-Gómez, Carmen Belen Alvarez-Simón, Jesús-José Ferré-Fernández, Francisco Sánchez-Sánchez, Jose Luis Sánchez-Sánchez, Jose Mª Garcia-Bueno, Sebastiá Sabater, Guadalupe Aparicio, Luis Miguel Antón-Aparicio, & Carmen Ramírez-Castillejo. (2013). C-Terminal-PEDF Reduces IC50 Doses and Chemoresistant Population of CD133 and BCRP1-Positve Cancer Stem Like Cells. Journal of Analytical Oncology, 2(4), 195–208. https://doi.org/10.6000/1927-7229.2013.02.04.2

Issue

Section

Articles