Expression and Function of Dipeptidyl Peptidase IV and Related Enzymes in Cancer

  • Petr Busek
  • Evzen Krepela
  • Vladislav Mares
  • Kvetoslava Vlasicova
  • Jan Sevcik
  • Aleksi Sedo
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (volume 575)


T98G Cell Dipeptidyl Peptidase Human Brain Microvascular Endothelial Cell Small Cell Lung Carcinoma Cell Anaplastic Thyroid Cancer Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abbott CA, Yu DM, Woollatt E, Sutherland GR, McCaughan GW, Gorrell MD, 2000, Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. Eur J Biochem. 267: 6140–6150.CrossRefPubMedGoogle Scholar
  2. Ariga N, Sato E, Ohuchi N, Nagura H, Ohtani H, 2001, Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast. Int J Cancer. 95: 67–72.CrossRefPubMedGoogle Scholar
  3. Bogenrieder T, Finstad CL, Freeman RH, Papandreou CN, Scher HI, Albino AP, Reuter VE, Nanus DM, 1997, Expression and localization of aminopeptidase A, aminopeptidase N, and dipeptidyl peptidase IV in benign and malignant human prostate tissue. Prostate. 33: 225–232.CrossRefPubMedGoogle Scholar
  4. Burger M, Glodek A, Hartmann T, Schmitt-Graff A, Silberstein LE, Fujii N, Kipps TJ, Burger JA, 2003, Functional expression of CXCR4 (CD184) on small-cell lung cancer cells mediates migration, integrin activation, and adhesion to stromal cells. Oncogene. 22: 8093–8101.CrossRefPubMedGoogle Scholar
  5. Busek P, Malik R, Sedo A, 2004, Dipeptidyl peptidase IV activity and/or structure homologues (DASH) and their substrates in cancer. Int J Biochem Cell Biol. 36: 408–421.CrossRefPubMedGoogle Scholar
  6. Cheng JD, Valianou M, Canutescu AA, Jaffe EK, Lee HO, Wang H, Lai JH, Bachovchin WW, Weiner LM, 2005, Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth. Mol Cancer Ther. 4: 351–60.CrossRefPubMedGoogle Scholar
  7. De Meester I, Durinx C, Bal G, Proost P, Struyf S, Goossens F, Augustyns K, Scharpe S, 2000, Natural substrates of dipeptidyl peptidase IV. Adv Exp Med Biol. 477: 67–87.PubMedCrossRefGoogle Scholar
  8. Duke-Cohan JS, Kim JH, Azouz A, 2004, Attractin: cautionary tales for therapeutic intervention in molecules with pleiotropic functionality. J. Environ Pathol Toxicol Oncol. 23: 1–11.CrossRefPubMedGoogle Scholar
  9. Goodman JD, Rozypal TL, Kelly T, 2003, Seprase, a membrane-bound protease, alleviates the serum growth requirement of human breast cancer cells. Clin Exp Metastasis 20: 459–470.CrossRefPubMedGoogle Scholar
  10. Hall JM, Korach KS, 2003, Stromal cell-derived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells. Mol Endocrinol. 17: 792–803.CrossRefPubMedGoogle Scholar
  11. Huang Y, Wang S, Kelly T, 2004, Seprase promotes rapid tumor growth and increased microvessel density in a mouse model of human breast cancer. Cancer Res. 64: 2712–6.CrossRefPubMedGoogle Scholar
  12. Hwang JH, Hwang JH, Chung HK, Kim DW, Hwang ES, Suh JM, Kim H, You KH, Kwon OY, Ro HK, Jo DY, Shong M, 2003, CXC chemokine receptor 4 expression and function in human anaplastic thyroid cancer cells. J Clin Endocrinol Metab. 88: 408–416.CrossRefPubMedGoogle Scholar
  13. Iwabuchi H, Toriya K, Mimura T, Tamai S, Ito K, Kato H, 1996, Staining for dipeptidyl aminopeptidase IV activity in nodular thyroid diseases. Acta Cytol. 40: 158–163.PubMedGoogle Scholar
  14. Iwasa S, Jin X, Okada K, Mitsumata M, Ooi A, 2003, Increased expression of seprase, a membrane-type serine protease, is associated with lymph node metastasis in human colorectal cancer. Cancer Lett. 199: 91–98.CrossRefPubMedGoogle Scholar
  15. Jensen JA, Carroll RE, Benya RV, 2001, The case for gastrin-releasing peptide acting as a morphogen when it and its receptor are aberrantly expressed in cancer. Peptides. 22: 689–699.CrossRefPubMedGoogle Scholar
  16. Jin X, Iwasa S, Okada K, Mitsumata M, Ooi A, 2003, Expression patterns of seprase, a membrane serine protease, in cervical carcinoma and cervical intraepithelial neoplasm. Anticancer Res. 23: 3195–3198.PubMedGoogle Scholar
  17. Kajiyama H, Kikkawa F, Suzuki T, Shibata K, Ino K, Mizutani S, 2002, Prolonged survival and decreased invasive activity attributable to dipeptidyl peptidase IV overexpression in ovarian carcinoma. Cancer Res. 62: 2753–2757.PubMedGoogle Scholar
  18. Kajiyama H, Kikkawa F, Khin E, Shibata K, Ino K, Mizutani S, 2003, Dipeptidyl peptidase IV overexpression induces up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases, resulting in decreased invasive potential in ovarian carcinoma cells. Cancer Res. 63: 2278–2283.PubMedGoogle Scholar
  19. Kelly T, Kechelava S, Rozypal TL, West KW, Korourian S, 1998, Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma cells of human breast cancers. Mod Pathol. 11: 855–63.PubMedGoogle Scholar
  20. Khin EE, Kikkawa F, Ino K, Kajiyama H, Suzuki T, Shibata K, Tamakoshi K, Nagasaka T, Mizutani S, 2003, Dipeptidyl peptidase IV expression in endometrial endometrioid adenocarcinoma and its inverse correlation with tumor grade. Am J Obstet Gynecol. 188: 670–676.CrossRefPubMedGoogle Scholar
  21. Kijima T, Maulik G, Ma PC, Tibaldi EV, Turner RE, Rollins B, Sattler M, Johnson BE, Salgia R, 2002, Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells. Cancer Res. 62: 6304–6311.PubMedGoogle Scholar
  22. Komatsu M, Urade M, Yamaoka M, Fukasawa K, Harada M, 1987, Alteration in dipeptidyl peptidase activities in cultured human carcinoma cells. J Natl Cancer Inst. 78: 863–868.PubMedGoogle Scholar
  23. Lambeir AM, Durinx C, Scharpe S, De Meester I, 2003, Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 40: 209–94.PubMedGoogle Scholar
  24. Lee BC, Lee TH, Avraham S, Avraham HK, 2004, Involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1alpha in breast cancer cell migration through human brain microvascular endothelial cells. Mol Cancer Res. 2: 327–338.PubMedGoogle Scholar
  25. Luboshits G, Shina S, Kaplan O, Engelberg S, Nass D, Lifshitz-Mercer B, Chaitchik S, Keydar I, Ben Baruch A, 1999, Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res. 59: 4681–4687.PubMedGoogle Scholar
  26. Mizokami Y, Kajiyama H, Shibata K, Ino K, Kikkawa F, Mizutani S, 2004, Stromal cell-derived factor-1alpha-induced cell proliferation and its possible regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma. Int J Cancer 110: 652–659.CrossRefPubMedGoogle Scholar
  27. Mochizuki H, Matsubara A, Teishima J, Mutaguchi K, Yasumoto H, Dahiya R, Usui T, Kamiya K, 2004, Interaction of ligand-receptor system between stromal-cell-derived factor-1 and CXC chemokine receptor 4 in human prostate cancer: a possible predictor of metastasis. Biochem Biophys Res Commun. 320: 656–663.CrossRefPubMedGoogle Scholar
  28. Monsky WL, Lin CY, Aoyama A, Kelly T, Akiyama SK, Mueller SC, Chen WT, 1994, A potential marker protease of invasiveness, seprase, is localized on invadopodia of human malignant melanoma cells. Cancer Res. 54: 5702–5710.PubMedGoogle Scholar
  29. Mori Y, Kono K, Matsumoto Y, Fujii H, Yamane T, Mitsumata M, Chen WT, 2004, The expression of a type II transmembrane serine protease (Seprase) in human gastric carcinoma. Oncology. 67: 411–419.CrossRefPubMedGoogle Scholar
  30. Mrowietz U, Schwenk U, Maune S, Bartels J, Kupper M, Fichtner I, Schroder JM, Schadendorf D, 1999, The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice. Br J Cancer. 79: 1025–1031.CrossRefPubMedGoogle Scholar
  31. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A, 2001, Involvement of chemokine receptors in breast cancer metastasis. Nature. 410: 50–56.CrossRefPubMedGoogle Scholar
  32. Murakami T, Maki W, Cardones AR, Fang H, Tun KA, Nestle FO, Hwang ST, 2002, Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Res. 62: 7328–7334.PubMedGoogle Scholar
  33. Nagakawa O, Ogasawara M, Murata J, Fuse H, Saiki I, 2001, Effect of prostatic neuropeptides on migration of prostate cancer cell lines. Int J Urol. 8: 65–70.CrossRefPubMedGoogle Scholar
  34. Okada K, Chen WT, Iwasa S, Jin X, Yamane T, Ooi A, Mitsumata M, 2003, Seprase, a membrane-type serine protease, has different expression patterns in intestinal-and diffuse-type gastric cancer. Oncology. 65: 363–370.CrossRefPubMedGoogle Scholar
  35. Palma C, Maggi CA, 2000, The role of tachykinins via NK1 receptors in progression of human gliomas. Life Sci. 67: 985–1001.CrossRefPubMedGoogle Scholar
  36. Qi SY, Riviere PJ, Trojnar J, Junien JL, Akinsanya KO, 2003, Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases. Biochem J. 373: 179–189.CrossRefPubMedGoogle Scholar
  37. Ramirez-Montagut T, Blachere NE, Sviderskaya EV, Bennett DC, Rettig WJ, Garin-Chesa P, Houghton AN, 2004, FAPalpha, a surface peptidase expressed during wound healing, is a tumor suppressor. Oncogene. 23: 5435–5446.CrossRefPubMedGoogle Scholar
  38. Reubi JC, Gugger M, Waser B, Schaer JC, 2001, Y(1)-mediated effect of neuropeptide Y in cancer: breast carcinomas as targets. Cancer Res. 61: 4636–4641.PubMedGoogle Scholar
  39. Reubi JC, 2003, Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 24: 389–427.CrossRefPubMedGoogle Scholar
  40. Scotton CJ, Wilson JL, Scott K, Stamp G, Wilbanks GD, Fricker S, Bridger G, Balkwill FR, 2002, Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res. 62: 5930–5938.PubMedGoogle Scholar
  41. Sedo A, Krepela E, Kasafirek E, 1989, A kinetic fluorometric assay of dipeptidyl peptidase IV in viable human blood mononuclear cells. Biochimie. 71: 757–761.CrossRefPubMedGoogle Scholar
  42. Sedo A, Krepela E, Kasafirek E, Kraml J, Kadlecova L, 1991, Dipeptidyl peptidase IV in the human lung and spinocellular lung cancer. Physiol Res. 40: 359–362.PubMedGoogle Scholar
  43. Sedo A, Malik R, 2001, Dipeptidyl peptidase IV-like molecules: homologous proteins or homologous activities? Biochim Biophys Acta. 1550: 107–116.PubMedGoogle Scholar
  44. Tseng WW, Liu CD, 2002, Peptide YY and cancer: current findings and potential clinical applications. Peptides. 23: 389–395.CrossRefPubMedGoogle Scholar
  45. Vanhoof G, Goossens F, De Meester I, Hendriks D, Scharpe S, 1995, Proline motifs in peptides and their biological processing. FASEB J. 9: 736–744.PubMedGoogle Scholar
  46. Wesley UV, Albino AP, Tiwari S, Houghton AN, 1999, A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. J Exp Med. 190: 311–322.CrossRefPubMedGoogle Scholar
  47. Wesley UV, Tiwari S, Houghton AN, 2004, Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells. Int J Cancer. 109: 855–866.CrossRefPubMedGoogle Scholar
  48. Wesley UV, McGroarty M, Homoyouni A, 2005, Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway. Cancer Res. 65: 1325–1334.CrossRefPubMedGoogle Scholar
  49. Wilson MJ, Ruhland AR, Quast BJ, Reddy PK, Ewing SL, Sinha AA, 2000, Dipeptidyl peptidase IV activities are elevated in prostate cancers and adjacent benign hyperplastic glands. J Androl. 21: 220–226.PubMedGoogle Scholar
  50. Zeelenberg IS, Ruuls-Van Stalle L, Roos E, 2003, The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. Cancer Res. 63: 3833–3839.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Petr Busek
    • 1
  • Evzen Krepela
    • 1
  • Vladislav Mares
    • 1
  • Kvetoslava Vlasicova
    • 1
  • Jan Sevcik
    • 1
  • Aleksi Sedo
    • 1
  1. 1.Joint Laboratory of Cancer Cell Biology of the 1st Faculty of MedicineCharles University Prague and the Institute of Physiology, Academy of SciencesPrague 2Czech Republic

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