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The effect of a novel frizzled 8-related antiproliferative factor on in vitro carcinoma and melanoma cell proliferation and invasion

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Summary

Antiproliferative factor (APF) is a potent frizzled protein 8-related sialoglycopeptide inhibitor of bladder epithelial cell proliferation that mediates its activity by binding to cytoskeletal associated protein 4 in the cell membrane. Synthetic asialylated APF (as-APF) (Galβ1-3GalNAcα-O-TVPAAVVVA) was previously shown to inhibit both normal bladder epithelial as well as T24 bladder carcinoma cell proliferation and heparin-binding epidermal growth factor-like growth factor (HB-EGF) production at low nanomolar concentrations, and an L-pipecolic acid derivative (Galβ1-3GalNAcα-O-TV-pipecolic acid-AAVVVA) was also shown to inhibit normal bladder epithelial cell proliferation. To better determine their spectrum of activity, we measured the effects of these APF derivatives on the proliferation of cells derived from additional urologic carcinomas (bladder and kidney), non-urologic carcinomas (ovary, lung, colon, pancreas, and breast), and melanomas using a 3H-thymidine incorporation assay. We also measured the effects of as-APF on cell HB-EGF and matrix metalloproteinase (MMP2) secretion plus cell invasion, using qRT-PCR, Western blot and an in vitro invasion assay. L-pipecolic acid as-APF and/or as-APF significantly inhibited proliferation of each cell line in a dose-dependent manner with IC50’s in the nanomolar range, regardless of tissue origin, cell type (carcinoma vs. melanoma), or p53 or ras mutation status. as-APF also inhibited HB-EGF and MMP2 production plus in vitro invasion of tested bladder, kidney, breast, lung, and melanoma tumor cell lines, in a dose-dependent manner (IC50 = 1–100 nM). Synthetic APF derivatives are potent inhibitors of urologic and non-urologic carcinoma plus melanoma cell proliferation, MMP2 production, and invasion, and may be useful for development as adjunctive antitumor therapy(ies).

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  3. Rosenberg JE, Carroll PR, Small EJ (2005) Update on chemotherapy for advanced bladder cancer. J Urol 174:14–20

    Article  PubMed  CAS  Google Scholar 

  4. Sengupta N, Siddiqui E, Mumtaz FH (2004) Cancers of the bladder. J R Soc Promot Health 124:228–229

    Article  PubMed  CAS  Google Scholar 

  5. Kaufman DS, Shipley WU, Feldman AS (2009) Bladder cancer. Lancet 374:239–249. doi:10.1016/So140-6736(09)60491-60498

    Article  PubMed  CAS  Google Scholar 

  6. Ward EM, Thun MJ, Hannan LM, Jemal A (2006) Interpreting cancer trends. Ann NY Acad Sci 1076:29–53

    Article  PubMed  Google Scholar 

  7. Miller AJ, Mihm MC Jr (2006) Mechanisms of disease: Melanoma. New Engl J Med 355:51–65

    Article  PubMed  CAS  Google Scholar 

  8. Thievessen I, Seifert HH, Swiatkowski S, Flori AR, Schulz WA (2003) E-cadherin involved in inactivation of WNT/beta-catenin signalling in urothelial carcinoma and normal urothelial cells. Br J Cancer 88:1932–1938

    Article  PubMed  CAS  Google Scholar 

  9. Bates RC, Mercurio AM (2005) The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther 4:365–370

    Article  PubMed  CAS  Google Scholar 

  10. Berx G, Van Roy F (2001) The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res 3:389–393

    Article  Google Scholar 

  11. Wakatsuki S, Watanabe R, Saito K, Saito T, Katagiri A, Sato S, Tomita Y (1996) Loss of human E-cadherin (ECD) correlated with invasiveness of transitional cell cancer in the renal pelvis, ureter and urinary bladder. Cancer Lett 103:11–17

    Article  PubMed  CAS  Google Scholar 

  12. Huber MA, Kraut N, Beug H (2005) Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 17:548–558

    Article  PubMed  CAS  Google Scholar 

  13. Guarino M, Rubino B, Ballabio G (2007) The role of epithelial-mesenchymal transition in cancer pathology. Pathology 39:305–318

    Article  PubMed  CAS  Google Scholar 

  14. Steelman LS, Stadelman KM, Chappell WH, Horn S, Bäsecke J, Cervello M, Nicoletti F, Libra M, Stivala F, Martelli AM, McCubrey JA (2008) Akt as a therapeutic target in cancer. Expert Opin Ther Targets 12:1139–1165

    Article  PubMed  CAS  Google Scholar 

  15. Grant S (2008) Co-targeting survival signalling pathways in cancer. J Clin Invest 118:3003–3006

    Article  PubMed  CAS  Google Scholar 

  16. Russo AE, Torrisi E, Bevelacqua Y, Perrotta R, Libra M, McCubrey JA, Spandidos DA, Stivala F, Malaponte G (2009) Melanoma: molecular pathogenesis and emerging target therapies. Int J Oncol 34:1481–1489

    PubMed  CAS  Google Scholar 

  17. Dreesen O, Brivanlou AH (2007) Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev 3:7–17

    Article  PubMed  CAS  Google Scholar 

  18. Miyamoto S, Yagi H, Yotsumoto F, Horiuchi S, Yoshizato T, Kawarabayashi T, Kuroki M, Mekada E (2007) New approach to cancer therapy: heparin binding-epidermal growth factor-like growth factor as a novel targeting molecule. Anticancer Res 27:3713–3721

    PubMed  CAS  Google Scholar 

  19. Kleiner DE, Stetler-Stevenson WG (1999) Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol 43(Suppl):S42–S51

    Article  PubMed  CAS  Google Scholar 

  20. Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67. doi:10.1016/j.cell.2010.03.015

    Article  PubMed  CAS  Google Scholar 

  21. Sonderegger S, Haslinger P, Sabri A, Leisser C, Otten JV, Fiala C, Knöfler M (2010) Wingless (Wnt)-3A induces trophoblast migration and matrix metalloproteinase-2 secretion through canonical Wnt signaling and protein kinase B/AKT activation. Endocrinology 151:211–220

    Article  PubMed  CAS  Google Scholar 

  22. Razandi M, Pedram A, Park ST, Levin ER (2003) Proximal events in signaling by plasma membrane estrogen receptors. J Biol Chem 278:2701–2712

    Article  PubMed  CAS  Google Scholar 

  23. Gould Rothberg BE, Bracken MB, Rimm DL (2009) Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst 101:452–474

    Article  PubMed  Google Scholar 

  24. Kanayama H, Yokota K, Kurokawa Y, Murakami Y, Nishitani M, Kagawa S (1998) Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in bladder cancer. Cancer 82:1359–1366

    Article  PubMed  CAS  Google Scholar 

  25. Keay SK, Szekely Z, Conrads TP, Veenstra TD, Barchi JJ Jr, Zhang C-O, Koch KR, Michejda CJ (2004) An antiproliferative factor from interstitial cystitis patients is a Frizzled 8 protein-related sialoglycopeptide. Proc Natl Acad Sci USA 101:11803–11808

    Article  PubMed  CAS  Google Scholar 

  26. Saitoh T, Hirai M, Katoh M (2001) Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2. Int J Oncol 18:991–996

    PubMed  CAS  Google Scholar 

  27. Rashid HH, Reeder JE, O’Connell MJ, Zhang CO, Messing EM, Keay SK (2004) Interstitial cystitis antiproliferative factor (APF) as a cell-cycle modulator. BMC Urol 4:3

    Article  PubMed  Google Scholar 

  28. Kim J, Keay SK, Dimitrakov JD, Freeman MR (2007) p53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells. FEBS Lett 581:3795–3799

    Article  PubMed  CAS  Google Scholar 

  29. Keay S, Seillier-Moiseiwitsch F, Zhang C-O, Chai TC, Zhang J (2003) Changes in human bladder cell gene expression associated with interstitial cystitis or antiproliferative factor treatment. Physiol Genomics 14:107–115

    PubMed  CAS  Google Scholar 

  30. Shahjee H, Koch K, Guo L, Zhang C-O, Keay S (2010) Antiproliferative factor decreases Akt phosphorylation and alters gene expression via CKAP4 in T24 bladder carcinoma cells. J Exp Clin Cancer Res 29:160–170

    Article  PubMed  CAS  Google Scholar 

  31. Kim J, Keay SK, Freeman MR (2009) Heparin-binding epidermal growth factor-like growth factor functionally antagonizes interstitial cystitis antiproliferative factor via mitogen-activated protein kinase pathway activation. BJU Int 103:541–546

    Article  PubMed  CAS  Google Scholar 

  32. Keay S, Kleinberg M, Zhang C-O, Hise MK, Warren JW (2000) Bladder epithelial cells from interstitial cystitis patients produce an inhibitor of HB-EGF production. J Urol 164:2112–2118

    Article  PubMed  CAS  Google Scholar 

  33. Kaczmarek P, Keay SK, Tocci GM, Koch KR, Zhang C-O, Barchi JJ Jr, Grkovic D, Guo L, Michejda CJ (2008) Structure-activity relationship studies for the peptide portion of the bladder epithelial cell antiproliferative factor from interstitial cystitis patients. J Med Chem 51:5974–5983

    Article  PubMed  CAS  Google Scholar 

  34. Planey SL, Keay SK, Zhang CO, Zacharias DA (2009) Palmitoylation of cytoskeleton associated protein 4 by DHHC2 regulates antiproliferative factor-mediated signaling. Mol Biol Cell 20:1454–1463

    Article  PubMed  CAS  Google Scholar 

  35. Mahnken A, Kausch I, Feller AC, Kruger S (2005) E-cadherin immunoreactivity correlates with recurrence and progression of minimally invasive transitional cell carcinomas of the urinary bladder. Oncol Rep 14:1065–1070

    PubMed  CAS  Google Scholar 

  36. Kashibuchi K, Tomita K, Schalken JA, Kume H, Yamaguchi T, Muto S, Horie S, Kitamura T (2006) The prognostic value of E-cadherin, alpha-, beta-, and gamma-catenin in urothelial cancer of the upper urinary tract. Eur Urol 49:839–845

    Article  PubMed  CAS  Google Scholar 

  37. Stein JP, Ginsberg DA, Grossfeld GD, Chatterjee SJ, Esrig D, Dickinson MG, Groshen S, Taylor CR, Jones PA, Skinner DG, Cote RJ (1998) Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer. J Natl Cancer Instit 90:1072–1079

    Article  CAS  Google Scholar 

  38. Slaton JW, Benedict WF, Dinney CP (2001) p53 in bladder cancer: mechanism of action, prognostic value, and target for therapy. Urology 57:852–859

    Article  PubMed  CAS  Google Scholar 

  39. Thøgersen VB, Sørensen BS, Poulsen SS, Orntoft TF, Wolf H, Nexo E (2001) A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients. Cancer Res 61:6227–6233

    PubMed  Google Scholar 

  40. Davies B, Waxman J, Wasan H, Abel P, Williams G, Krausz T, Neal D, Thomas D, Hanby A, Balkwill F (1993) Levels of matrix metalloproteases in bladder cancer correlate with tumor grade and invasion. Cancer Res 53:5365–5369

    PubMed  CAS  Google Scholar 

  41. Ching CB, Hansel DE (2010) Expanding therapeutic targets in bladder cancer: the PI3K/Akt/mTOR pathway. Lab Invest 90:1406–1414

    Article  PubMed  CAS  Google Scholar 

  42. Cooper MJ, Haluschak JJ, Johnson D, Schwartz S, Morrison LJ, Lippa M, Hatzivassiliou G, Tan J (1994) p53 mutations in bladder carcinoma cell lines. Oncol Res 6:569–579

    PubMed  CAS  Google Scholar 

  43. Sanchez-Carbayo M, Socci ND, Charytonowicz E, Lu M, Prystowsky M, Childs G, Cordon-Cardo C (2002) Molecular profiling of bladder cancer using cDNA microarrays: defining histogenesis and biological phenotypes. Cancer Res 62:6973–6980

    PubMed  CAS  Google Scholar 

  44. Smith H, Weaver D, Barjenbruch O, Weinstein S, Ross G Jr (1989) Routine excretory urography in follow-up of superficial transitional cell carcinoma of bladder. Urology 34:193–196

    Article  PubMed  CAS  Google Scholar 

  45. Porta C, Figlin RA (2009) Phosphatidylinositol-3-kinase/Akt signaling pathway and kidney cancer, and the therapeutic potential of phosphatidylinositol-3-kinase/Akt inhibitors. J Urol 182:2569–2577

    Article  PubMed  CAS  Google Scholar 

  46. Park JY, Lin PY, Weiss RH (2007) Targeting the PI3K-Akt pathway in kidney cancer. Expert Rev Anticancer Ther 7:863–870

    Article  PubMed  CAS  Google Scholar 

  47. Bjelogrlic SK, Radulovic S, Babovic N (2008) Molecular targeting agents in renal cell carcinoma: present strategies and future perspectives. Curr Pharm Des 14:1058–1077

    Article  PubMed  CAS  Google Scholar 

  48. Herbst RS, Hermach JV, Lippman RM (2008) Molecular origins of cancer – lung cancer. N Engl J Med 359:1367–1380

    Article  PubMed  CAS  Google Scholar 

  49. “Lung Carcinoma: Tumors of the Lungs”. Merck manual professional edition, online edition. http://www.merck.com/mmpe/sec05/ch062/ch062b.html#sec05-ch062-ch062b-1405

  50. Oren M (2003) Decision making by p53: life, death, and cancer. Cell Death Differ 10:431–442

    Article  PubMed  CAS  Google Scholar 

  51. Campling BG, El-Deiry WS (2003) Clinical implication of p53 mutation in lung cancer. Mol Biotech 24:141–156

    Article  CAS  Google Scholar 

  52. Leinonen T, Pirinen R, Böhm J, Johansson R, Kosma VM (2008) Increased expression of matrix metalloproteinase-2 (MMP-2) predicts tumour recurrence and unfavourable outcome in non-small cell lung cancer. Histol Histopathol 23:693–700

    PubMed  Google Scholar 

  53. Soussi T (2000) The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann NY Acad Sci 910:121–137

    Article  PubMed  CAS  Google Scholar 

  54. Milyavsky M, Tabach Y, Shats I, Erez N, Cohen Y, Tang X, Kalis M, Kogan I, Buganim Y, Goldfinger N, Ginsberg D, Harris CC, Domany E, Rotter V (2005) Transcriptional programs following genetic alterations in p53, INK4A, and H-Ras genes along defined stages of malignant transformation. Cancer Res 65:4530–4543. doi:10.1158/0008-5472.CAN-04-3880

    Article  PubMed  CAS  Google Scholar 

  55. Manning BD, Cantley LC (2007) AKT/PKB signaling: navigating downstream. Cell 129:1261–1274

    Article  PubMed  CAS  Google Scholar 

  56. von Lintig FC, Dreilinger AD, Varki NM, Wallace AM, Casteel DE, Boss GR (2000) Ras activation in human breast cancer. Breast Cancer Res Treat 62:51–62

    Article  Google Scholar 

  57. Krontiris TG, Devlin B, Karp DD, Robert NJ, Risch N (1993) An association between the risk of cancer and mutations in the HRAS1 minisatellite locus. N Engl J Med 329:517–523

    Article  PubMed  CAS  Google Scholar 

  58. Oliveira AM, Ross JS, Fletcher JA (2005) Tumor suppressor genes in breast cancer: the gatekeepers and the caretakers. Am J Clin Pathol 124(Suppl):S16–S28

    PubMed  CAS  Google Scholar 

  59. Jezierska A, Motyl T (2009) Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit 15:RA32-40

    Google Scholar 

  60. Hernandez-Aya LF, Gonzalez-Angulo AM (2011) Targeting the phosphatidylinositol 3-kinase signaling pathway in breast cancer. Oncologist 16:404–414

    Article  PubMed  CAS  Google Scholar 

  61. Duffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, Lamerz R, Peltomaki P, Sturgeon C, Topolcan O (2007) Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer 43:1348–1360

    Article  PubMed  CAS  Google Scholar 

  62. Yamamoto S, Tomita Y, Hoshida Y, Morooka T, Nagano H, Dono K, Umeshita K, Sakon M, Ishikawa O, Ohigashi H, Nakamori S, Monden M, Aozasa K (2004) Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma. Clin Cancer Res 10:2846–2850

    Article  PubMed  CAS  Google Scholar 

  63. Juuti A, Lundin J, Nordling S, Louhimo J, Haglund C (2006) Epithelial MMP-2 expression correlates with worse prognosis in pancreatic cancer. Oncology 71:61–68

    Article  PubMed  CAS  Google Scholar 

  64. Mihaljevic AL, Michalski CW, Friess H, Kleeff J (2010) Molecular mechanism of pancreatic cancer--understanding proliferation, invasion, and metastasis. Langenbecks Arch Surg 395:295–308

    Article  PubMed  Google Scholar 

  65. Baxter LL, Loftus SK, Pavan WJ (2009) Networks and pathways in pigmentation, health, and disease. Wiley Interdiscip Rev Syst Biol Med 1:359–371

    Article  PubMed  CAS  Google Scholar 

  66. Om A, Ghose T, Rowden G (1991) Keratin and carcinoembryonic antigen (CEA) in human melanoma cells. Virchows Arch B Cell Pathol 61:81–87

    CAS  Google Scholar 

  67. Selby WL, Nance KV, Park HK (1992) CEA immunoreactivity in metastatic malignant melanoma. Mod Pathol 5:415–419

    PubMed  CAS  Google Scholar 

  68. Palmieri G, Capone M, Ascierto ML, Gentilcore G, Stroncek DF, Casula M, Sini MC, Palla M, Mozzillo N, Ascierto PA (2009) Main roads to melanoma. J Translat Med 7:86–102. doi:10.1186/1479-5876-7-86

    Article  Google Scholar 

  69. Yamamoto H, Itoh F, Iku S, Adachi Y, Fukushima H, Sasaki S, Mukaiya M, Hirata K, Imai K (2001) Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 19:1118–1127

    PubMed  CAS  Google Scholar 

  70. Yadav V, Denning MF (2011) Fyn is induced by Ras/PI3K/Akt signaling and is required for enhanced invasion/migration. Mol Carcinog 50:346–352. doi:10.1002/mc.20716

    Article  PubMed  CAS  Google Scholar 

  71. McKenna WG, Muschel RJ, Gupta AK, Hahn SM, Bernhard EJ (2003) The RAS signal transduction pathway and its role in radiation sensitivity. Oncogene 22:5866–5875. doi:10.1038/sj.onc.1206699

    Article  PubMed  CAS  Google Scholar 

  72. Chautard E, Loubeau G, Tchirkov A, Chassagne J, Vermot-Desroches C, Morel L, Verrelle P (2010) Akt signaling pathway: a target for radiosensitizing human malignant glioma. Neuro Oncol 12:434–443

    PubMed  CAS  Google Scholar 

  73. Gupta AK, Cerniglia GJ, Mick R, Ahmed MS, Bakanauskas VJ, Muschel RJ, McKenna WG (2003) Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. Int J Radiat Oncol Biol Phys 56:846–853

    Article  PubMed  CAS  Google Scholar 

  74. Krasny L, Shimony N, Tzukert K, Gorodetsky R, Lecht S, Nettelbeck DM, Haviv YS (2010) An in-vitro tumour microenvironment model using adhesion to type I collagen reveals Akt-dependent radiation resistance in renal cancer cells. Nephrol Dial Transplant 25:373–380

    Article  PubMed  CAS  Google Scholar 

  75. Gottschalk AR, Doan A, Nakamura JL, Stokoe D, Haas-Kogan DA (2005) Inhibition of phosphatidylinositol-3-kinase causes increased sensitivity to radiation through a PKB-dependent mechanism. Int J Radiat Oncol Biol Phys 63:1221–1227

    Article  PubMed  CAS  Google Scholar 

  76. Xia S, Yu S, Fu Q, Liu F, Zheng W, Fu X, Zhao Y (2010) Inhibiting PI3K/Akt pathway increases DNA damage of cervical carcinoma HeLa cells by drug radiosensitization. J Huazhong Univ Sci Technolog Med Sci 30:360–364

    Article  PubMed  CAS  Google Scholar 

  77. Schuurbiers OC, Kaanders JH, van der Heijden HF, Dekhuijzen RP, Oyen WJ, Bussink J (2009) The PI3-K/AKT-pathway and radiation resistance mechanisms in non-small cell lung cancer. J Thorac Oncol 4:761–767

    Article  PubMed  Google Scholar 

  78. Toulany M, Kehlbach R, Florczak U, Sak A, Wang S, Chen J, Lobrich M, Rodemann HP (2008) Targeting of AKT1 enhances radiation toxicity of human tumor cells by inhibiting DNA-PKcs-dependent DNA double-strand break repair. Mol Cancer Ther 7:1771–1781

    Article  Google Scholar 

  79. Johnson GE, Ivanov VN, Hei TK (2008) Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis 13:790–802

    Article  PubMed  CAS  Google Scholar 

  80. Liebmann J, Cook JA, Fisher J, Teague D, Mitchell JB (1994) In vitro studies of Taxol as a radiation sensitizer in human tumor cells. J Natl Cancer Inst 86:441–446

    Article  PubMed  CAS  Google Scholar 

  81. Conrads TP, Tocci GM, Hood BL, Zhang CO, Guo L, Koch KR, Michejda CJ, Veenstra TD, Keay SK (2006) CKAP4/p63 is a receptor for the frizzled-8 protein-related antiproliferative factor from interstitial cystitis patients. J Biol Chem 281:37836–37843

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors thank Stewart Martin, Greenebaum Cancer Center and the University of Maryland School of Medicine, for providing some of the breast carcinoma cell lines, and Eunice Katz for assistance with the preparation of this manuscript. This material is based upon work supported by the Office of Research and Development (Medical Research Service), Department of Veterans Affairs, as well as funding from the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We also gratefully acknowledge the assistance of the Biophysics Resource in the Structural Biophysics Laboratory, at the Center for Cancer Research, National Cancer Institute.

Disclosures

Susan Keay and Piotr Kaczmarek are named as inventors on patents involving APF.

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Authors and Affiliations

  1. Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Kristopher R. Koch, Li Guo, Hanief M. Shahjee & Susan Keay

  2. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Chen-Ou Zhang

  3. Chemical Biology Laboratory, National Cancer Institute at Frederick, Frederick, MD, 21702, USA

    Piotr Kaczmarek & Joseph Barchi Jr.

  4. Veterans Administration Maryland Health Care System, Baltimore, MD, 21201, USA

    Susan Keay

  5. VA Medical Center, Room 3B-184, 10 N. Greene Street, Baltimore, MD, 21201, USA

    Susan Keay

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  1. Kristopher R. Koch
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  2. Chen-Ou Zhang
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  7. Susan Keay
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Correspondence to Susan Keay.

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Koch, K.R., Zhang, CO., Kaczmarek, P. et al. The effect of a novel frizzled 8-related antiproliferative factor on in vitro carcinoma and melanoma cell proliferation and invasion. Invest New Drugs 30, 1849–1864 (2012). https://doi.org/10.1007/s10637-011-9746-x

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