An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer

Oncotarget

Volumn 6, Issue 28, 2015, Pages 24947-24968

  Liao, Mei Ying ^a,b   Lai, Jun Kai ^a   Kuo, Mark Yen Ping ^b   Lu, Ruei Min ^a   Lin, Cheng Wei ^a   Cheng, Ping Chang ^a   Liang, Kang Hao ^a   Wu, Han Chung ^a,c  

^a INSTITUTE OF CELLULAR AND ORGANISMIC BIOLOGY   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^c GENOMICS RESEARCH CENTER   (Taiwan)

Author keywords

Cancer therapy; Colorectal carcinoma; EpCAM; Targeting imaging; Therapeutic antibody

Indexed keywords

EPAB2 6; EPITHELIAL CELL ADHESION MOLECULE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; IRINOTECAN; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; CAMPTOTHECIN; CELL ADHESION MOLECULE; TUMOR ANTIGEN; VITAMIN B COMPLEX;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; BREAST CANCER CELL LINE; CANCER CELL LINE; CANCER IMMUNOTHERAPY; CANCER INHIBITION; CANCER PROGNOSIS; COLON CANCER; COLORECTAL CANCER CELL LINE; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENTIATION; DRUG PROTEIN BINDING; FEMALE; HUMAN; HUMAN CELL; LUNG CANCER CELL LINE; METASTASIS POTENTIAL; MOUSE; MOUSE MODEL; NASOPHARYNX CARCINOMA; NONHUMAN; ORAL CANCER CELL LINE; OVARIAN CANCER CELL LINE; OVERALL SURVIVAL; PANCREAS CANCER; PANCREATIC CANCER CELL LINE; PROTEIN DOMAIN; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL SURVIVAL; COLONIC NEOPLASMS; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; FLOW CYTOMETRY; HCT 116 CELL LINE; IMMUNOLOGY; METABOLISM; MOLECULARLY TARGETED THERAPY; NONOBESE DIABETIC MOUSE; PATHOLOGY; PROCEDURES; SCID MOUSE; TUMOR CELL LINE; WESTERN BLOTTING;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, NEOPLASM; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BLOTTING, WESTERN; CAMPTOTHECIN; CELL ADHESION MOLECULES; CELL LINE, TUMOR; CELL SURVIVAL; COLONIC NEOPLASMS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SYNERGISM; EPITHELIAL CELL ADHESION MOLECULE; FLOW CYTOMETRY; FLUOROURACIL; HCT116 CELLS; HUMANS; LEUCOVORIN; MICE, INBRED NOD; MICE, SCID; MOLECULAR TARGETED THERAPY; VITAMIN B COMPLEX; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84944463696     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.4453     Document Type: Article

References (81)

1. Balzar M, Prins FA, Bakker HA, Fleuren GJ, Warnaar SO, Litvinov SV. The structural analysis of adhesions mediated by Ep-CAM. Exp Cell Res. 1999; 246:108-121.
2. de Boer CJ, van Krieken JH, Janssen-van Rhijn CM, Litvinov SV. Expression of Ep-CAM in normal, regenerating, metaplastic, and neoplastic liver. J Pathol. 1999; 188:201-206.
3. Ni J, Cozzi P, Hao J, Beretov J, Chang L, Duan W, Shigdar S, Delprado W, Graham P, Bucci J, Kearsley J, Li Y. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/ radioresistance via the PI3K/Akt/mTOR signaling pathway. The international journal of biochemistry & cell biology. 2013; 45:2736-2748.
4. Gastl G, Spizzo G, Obrist P, Dunser M, Mikuz G. Ep-CAM overexpression in breast cancer as a predictor of survival. Lancet. 2000; 356:1981-1982.
5. Patriarca C, Macchi RM, Marschner AK, Mellstedt H. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer treatment reviews. 2012; 38:68-75.
6. Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, Kononen J, Simon R, Sauter G, Baeuerle PA. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer. 2006; 94:128-135.
7. Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, Herold CI, Marcom PK, George DJ, Garcia-Blanco MA. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res. 2011; 9:997-1007.
8. Simon M, Stefan N, Pluckthun A, Zangemeister-Wittke U. Epithelial cell adhesion molecule-targeted drug delivery for cancer therapy. Expert opinion on drug delivery. 2013; 10:451-468.
9. Punt CJ, Nagy A, Douillard JY, Figer A, Skovsgaard T, Monson J, Barone C, Fountzilas G, Riess H, Moylan E, Jones D, Dethling J, Colman J, Coward L, MacGregor S. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Lancet. 2002; 360:671-677.
10. Schmidt M, Scheulen ME, Dittrich C, Obrist P, Marschner N, Dirix L, Schmidt M, Ruttinger D, Schuler M, Reinhardt C, Awada A. An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO. 2010; 21:275-282.
11. Cioffi M, Dorado J, Baeuerle PA, Heeschen C. EpCAM/ CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. Clin Cancer Res. 2012; 18:465-474.
12. Sears HF, Atkinson B, Mattis J, Ernst C, Herlyn D, Steplewski Z, Hayry P, Koprowski H. Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours. Lancet. 1982; 1:762-765.
13. Riethmuller G, Holz E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Funke I, Pichlmaier H, Hirche H, Buggisch P, Witte J, Pichlmayr R. Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 1998; 16:1788-1794.
14. Riethmuller G, Schneider-Gadicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, et al. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet. 1994; 343:1177-1183.
15. de Bono JS, Tolcher AW, Forero A, Vanhove GF, Takimoto C, Bauer RJ, Hammond LA, Patnaik A, White ML, Shen S, Khazaeli MB, Rowinsky EK, LoBuglio AF. ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced adenocarcinomas. Clin Cancer Res. 2004; 10:7555-7565.
16. Zeidler R, Reisbach G, Wollenberg B, Lang S, Chaubal S, Schmitt B, Lindhofer H. Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing. J Immunol. 1999; 163:1246-1252.
17. Brischwein K, Schlereth B, Guller B, Steiger C, Wolf A, Lutterbuese R, Offner S, Locher M, Urbig T, Raum T, Kleindienst P, Wimberger P, Kimmig R, Fichtner I, Kufer P, Hofmeister R, et al. MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Molecular immunology. 2006; 43:1129-1143.
18. Di Paolo C, Willuda J, Kubetzko S, Lauffer I, Tschudi D, Waibel R, Pluckthun A, Stahel RA, Zangemeister-Wittke U. A recombinant immunotoxin derived from a humanized epithelial cell adhesion molecule-specific single-chain antibody fragment has potent and selective antitumor activity. Clin Cancer Res. 2003; 9:2837-2848.
19. Xiang R, Lode HN, Dolman CS, Dreier T, Varki NM, Qian X, Lo KM, Lan Y, Super M, Gillies SD, Reisfeld RA. Elimination of established murine colon carcinoma metastases by antibody-interleukin 2 fusion protein therapy. Cancer research. 1997; 57:4948-4955.
20. Baeuerle PA, Gires O. EpCAM (CD326) finding its role in cancer. Br J Cancer. 2007; 96:417-423.
21. Ruf P, Gires O, Jager M, Fellinger K, Atz J, Lindhofer H. Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer. Br J Cancer. 2007; 97:315-321.
22. Naundorf S, Preithner S, Mayer P, Lippold S, Wolf A, Hanakam F, Fichtner I, Kufer P, Raum T, Riethmuller G, Baeuerle PA, Dreier T. In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment. Int J Cancer. 2002; 100:101-110.
23. Schwartzberg LS. Clinical experience with edrecolomab: a monoclonal antibody therapy for colorectal carcinoma. Critical reviews in oncology/hematology. 2001; 40:17-24.
24. Kurtz JE, Dufour P. Adecatumumab: an anti-EpCAM monoclonal antibody, from the bench to the bedside. Expert opinion on biological therapy. 2010; 10:951-958.
25. Strnad J, Hamilton AE, Beavers LS, Gamboa GC, Apelgren LD, Taber LD, Sportsman JR, Bumol TF, Sharp JD, Gadski RA. Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA. Cancer research. 1989; 49:314-317.
26. Simon B, Podolsky DK, Moldenhauer G, Isselbacher KJ, Gattoni-Celli S, Brand SJ. Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein. Proceedings of the National Academy of Sciences of the United States of America. 1990; 87:2755-2759.
27. Szala S, Kasai Y, Steplewski Z, Rodeck U, Koprowski H, Linnenbach AJ. Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens. Proceedings of the National Academy of Sciences of the United States of America. 1990; 87:6833-6837.
28. Chong JM, Speicher DW. Determination of disulfide bond assignments and N-glycosylation sites of the human gastrointestinal carcinoma antigen GA733-2 (CO17-1A, EGP, KS1-4, KSA, and Ep-CAM. The Journal of biological chemistry. 2001; 276:5804-5813.
29. Molina F, Bouanani M, Pau B, Granier C. Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families. European journal of biochemistry / FEBS. 1996; 240:125-133.
30. Meh P, Pavsic M, Turk V, Baici A, Lenarcic B. Dual concentration-dependent activity of thyroglobulin type-1 domain of testican: specific inhibitor and substrate of cathepsin L. Biological chemistry. 2005; 386:75-83.
31. Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, Turk D. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochimica et biophysica acta. 2012; 1824:68-88.
32. Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Munz M, Gires O. Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009; 11:162-171.
33. Hachmeister M, Bobowski KD, Hogl S, Dislich B, Fukumori A, Eggert C, Mack B, Kremling H, Sarrach S, Coscia F, Zimmermann W, Steiner H, Lichtenthaler SF, Gires O. Regulated intramembrane proteolysis and degradation of murine epithelial cell adhesion molecule mEpCAM. PloS one. 2013; 8:e71836.
34. Lin CW, Liao MY, Lin WW, Wang YP, Lu TY, Wu HC. Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer. The Journal of biological chemistry. 2012; 287:39449-39459.
35. Lu TY, Lu RM, Liao MY, Yu J, Chung CH, Kao CF, Wu HC. Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. The Journal of biological chemistry. 2010; 285:8719-8732.
36. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008; 8:755-768.
37. Gires O, Klein CA, Baeuerle PA. On the abundance of EpCAM on cancer stem cells. Nat Rev Cancer. 2009; 9:143. author reply 143.
38. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, Reid LM, Minato H, Honda M, Kaneko S, Tang ZY, Wang XW. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009; 136:1012-1024.
39. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007; 450:1235-1239.
40. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004; 10:6897-6904.
41. Deng G, Herrler M, Burgess D, Manna E, Krag D, Burke JF. Enrichment with anti-cytokeratin alone or combined with anti-EpCAM antibodies significantly increases the sensitivity for circulating tumor cell detection in metastatic breast cancer patients. Breast cancer research: BCR. 2008; 10:R69.
42. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009; 138:645-659.
43. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007; 1:313-323.
44. Chiba T, Kita K, Zheng YW, Yokosuka O, Saisho H, Iwama A, Nakauchi H, Taniguchi H. Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 2006; 44:240-251.
45. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF. Phenotypic characterization of human colorectal cancer stem cells. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104:10158-10163.
46. Lin CT, Chan WY, Chen W, Huang HM, Wu HC, Hsu MM, Chuang SM, Wang CC. Characterization of seven newly established nasopharyngeal carcinoma cell lines. Lab Invest. 1993; 68:716-727.
47. Lo A, Lin CT, Wu HC. Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery. Molecular cancer therapeutics. 2008; 7:579-589.
48. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975; 256:495-497.
49. Tung KH, Lin CW, Kuo CC, Li LT, Kuo YH, Wu HC. CHC promotes tumor growth and angiogenesis through regulation of HIF-1alpha and VEGF signaling. Cancer Lett. 2013; 331:58-67.
50. Liu IJ, Chiu CY, Chen YC, Wu HC. Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus. The Journal of biological chemistry. 2011; 286:9726-9736.
51. Pavsic M, Guncar G, Djinovic-Carugo K, Lenarcic B. Crystal structure and its bearing towards an understanding of key biological functions of EpCAM. Nature communications. 2014; 5:4764.
52. Munz M, Murr A, Kvesic M, Rau D, Mangold S, Pflanz S, Lumsden J, Volkland J, Fagerberg J, Riethmuller G, Ruttinger D, Kufer P, Baeuerle PA, Raum T. Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies. Cancer cell international. 2010; 10:44.
53. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350:2335-2342.
54. Ocvirk J, Brodowicz T, Wrba F, Ciuleanu TE, Kurteva G, Beslija S, Koza I, Papai Z, Messinger D, Yilmaz U, Faluhelyi Z, Yalcin S, Papamichael D, Wenczl M, Mrsic-Krmpotic Z, Shacham-Shmueli E, et al. Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial. World journal of gastroenterology: WJG. 2010; 16:3133-3143.
55. Fanciullino R, Giacometti S, Mercier C, Aubert C, Blanquicett C, Piccerelle P, Ciccolini J. In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation. Br J Cancer. 2007; 97:919-926.
56. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA: a cancer journal for clinicians. 2010; 60:277-300.
57. Akita H, Nagano H, Takeda Y, Eguchi H, Wada H, Kobayashi S, Marubashi S, Tanemura M, Takahashi H, Ohigashi H, Tomita Y, Ishikawa O, Mori M, Doki Y. Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity. Oncogene. 2011; 30:3468-3476.
58. Fong D, Steurer M, Obrist P, Barbieri V, Margreiter R, Amberger A, Laimer K, Gastl G, Tzankov A, Spizzo G. Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance. Journal of clinical pathology. 2008; 61:31-35.
59. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004; 363:1049-1057.
60. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 1997; 15:2403-2413.
61. Chaudry MA, Sales K, Ruf P, Lindhofer H, Winslet MC. EpCAM an immunotherapeutic target for gastrointestinal malignancy: current experience and future challenges. Br J Cancer. 2007; 96:1013-1019.
62. Liao MY, Kuo MY, Lu TY, Wang YP, Wu HC. Generation of an anti-EpCAM antibody and epigenetic regulation of EpCAM in colorectal cancer. International journal of oncology. 2015; .
63. Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009; 9:701-713.
64. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991; 253:49-53.
65. Ralhan R, He HC, So AK, Tripathi SC, Kumar M, Hasan MR, Kaur J, Kashat L, MacMillan C, Chauhan SS, Freeman JL, Walfish PG. Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers. PloS one. 2010; 5:e14130.
66. Maaser K, Borlak J. A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators. Br J Cancer. 2008; 99:1635-1643.
67. Sankpal NV, Willman MW, Fleming TP, Mayfield JD, Gillanders WE. Transcriptional repression of epithelial cell adhesion molecule contributes to p53 control of breast cancer invasion. Cancer research. 2009; 69:753-757.
68. Huang HP, Chen PH, Yu CY, Chuang CY, Stone L, Hsiao WC, Li CL, Tsai SC, Chen KY, Chen HF, Ho HN, Kuo HC. Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency reprogramming. The Journal of biological chemistry. 2011; 286:33520-33532.
69. Liu M, Casimiro MC, Wang C, Shirley LA, Jiao X, Katiyar S, Ju X, Li Z, Yu Z, Zhou J, Johnson M, Fortina P, Hyslop T, Windle JJ, Pestell RG. p21CIP1 attenuates Rasand c-Myc-dependent breast tumor epithelial mesenchymal transition and cancer stem cell-like gene expression in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2009; 106:19035-19039.
70. Yamashita T, Budhu A, Forgues M, Wang XW. Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma. Cancer research. 2007; 67:10831-10839.
71. Driemel C, Kremling H, Schumacher S, Will D, Wolters J, Lindenlauf N, Mack B, Baldus SA, Hoya V, Pietsch JM, Panagiotidou P, Raba K, Vay C, Vallbohmer D, Harreus U, Knoefel WT, et al. Context-dependent adaption of EpCAM expression in early systemic esophageal cancer. Oncogene. 2014; 33:4904-4915.
72. Schulze K, Gasch C, Staufer K, Nashan B, Lohse AW, Pantel K, Riethdorf S, Wege H. Presence of EpCAMpositive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma. Int J Cancer. 2013; 133:2165-2171.
73. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000; 343:905-914.
74. Fields AL, Keller A, Schwartzberg L, Bernard S, Kardinal C, Cohen A, Schulz J, Eisenberg P, Forster J, Wissel P. Adjuvant therapy with the monoclonal antibody Edrecolomab plus fluorouracil-based therapy does not improve overall survival of patients with stage III colon cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2009; 27:1941-1947.
75. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, Denicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009; 324:1457-1461.
76. Welch SA, Moore MJ. Combination chemotherapy in advanced pancreatic cancer: time to raise the white flag? Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2007; 25:2159-2161.
77. Nomura T, Katunuma N. Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. J Med Invest. 2005; 52:1-9.
78. Riedle S, Kiefel H, Gast D, Bondong S, Wolterink S, Gutwein P, Altevogt P. Nuclear translocation and signalling of L1-CAM in human carcinoma cells requires ADAM10 and presenilin/gamma-secretase activity. The Biochemical journal. 2009; 420:391-402.
79. Mechtersheimer S, Gutwein P, Agmon-Levin N, Stoeck A, Oleszewski M, Riedle S, Postina R, Fahrenholz F, Fogel M, Lemmon V, Altevogt P. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. The Journal of cell biology. 2001; 155:661-673.
80. Fagotto F, Gumbiner BM. Cell contact-dependent signaling. Developmental biology. 1996; 180:445-454.
81. Denzel S, Maetzel D, Mack B, Eggert C, Barr G, Gires O. Initial activation of EpCAM cleavage via cell-to-cell contact. BMC Cancer. 2009; 9:402.