Cancer Immunology, Immunotherapy

, 58:1419 | Cite as

Amyloid precursor-like protein 2 association with HLA class I molecules

  • Amit Tuli
  • Mahak Sharma
  • Xiaojian Wang
  • Laura C. Simone
  • Haley L. Capek
  • Steven Cate
  • William H. Hildebrand
  • Naava Naslavsky
  • Steve Caplan
  • Joyce C. Solheim
Original Article

Abstract

Amyloid precursor-like protein 2 (APLP2) is a ubiquitously expressed protein. The previously demonstrated functions for APLP2 include binding to the mouse major histocompatibility complex (MHC) class I molecule H-2Kd and down regulating its cell surface expression. In this study, we have investigated the interaction of APLP2 with the human leukocyte antigen (HLA) class I molecule in human tumor cell lines. APLP2 was readily detected in pancreatic, breast, and prostate tumor lines, although it was found only in very low amounts in lymphoma cell lines. In a pancreatic tumor cell line, HLA class I was extensively co-localized with APLP2 in vesicular compartments following endocytosis of HLA class I molecules. In pancreatic, breast, and prostate tumor lines, APLP2 was bound to the HLA class I molecule. APLP2 was found to bind to HLA-A24, and more strongly to HLA-A2. Increased expression of APLP2 resulted in reduced surface expression of HLA-A2 and HLA-A24. Overall, these studies demonstrate that APLP2 binds to the HLA class I molecule, co-localizes with it in intracellular vesicles, and reduces the level of HLA class I molecule cell surface expression.

Keywords

Amyloid precursor-like protein 2 Antigen presentation Human leukocyte antigen Major histocompatibility complex class I Tumor 

Notes

Acknowledgments

We thank Dr. Shantaram Joshi, Dr. Kenneth Cowan, Dr. Vinod Labhasetwar, Dr. Michael A. Hollingsworth, Dr. Richard MacDonald, Dr. John Chan, Vivek Gautam, Christopher Connelly, Michelle Hartman, Himabindu Ramachandrareddy, Jaspreet Vasir, Tom Caffrey, Dr. Pankaj Singh, Dr. Wendy Maury, and Dr. Ted Hansen for their assistance with obtaining cell lines and antibodies, and we thank Dr. Atsunori Hiasa and Dr. Hiroshi Shiku for the HLA-A*2404 cDNA. We gratefully acknowledge the assistance of the personnel of the UNMC Cell Analysis Facility and the Monoclonal Antibody Facility. Core facilities at UNMC receive support from the NIH Cancer Center Support Grant P30CA036727. This work was supported by NIH Grants GM57428 (to J.C.S.) and GM74876 (to S.C.), an Eppley Cancer Center Pediatric Cancer Research Grant, UNMC Graduate Studies Fellowships (to A.T., M.S., and L.S.), a Nebraska Center for Cellular Signaling Fellowship and an American Heart Association Predoctoral Fellowship (to M.S.), an NIH Training Grant T32 CA009476 Fellowship (to L.S.), and a Graduate Assistance in Areas of National Need Fellowship (to H.C.).

References

  1. 1.
    Abba MC, Drake JA, Hawkins KA, Hu Y, Sun H, Notcovich C, Gaddis S, Sahin A, Baggerly K, Marcelo Aldaz C (2004) Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression. Breast Cancer Res 6:499–513CrossRefGoogle Scholar
  2. 2.
    Anliker B, Müller U (2006) The functions of mammalian amyloid precursor protein and related amyloid precursor-like proteins. Neurodegener Dis 3:239–246PubMedCrossRefGoogle Scholar
  3. 3.
    Cailleau R, Olive M, Cruciger OV (1978) Long-term human breast carcinoma cell lines of metastatic origin: preliminary characterization. In Vitro 17:911–915CrossRefGoogle Scholar
  4. 4.
    Campoli M, Ferrone S (2008) HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene 27:5869–5885PubMedCrossRefGoogle Scholar
  5. 5.
    Caplan S, Naslavsky N, Hartnell LM, Lodge R, Polishchuk RS, Donaldson JG, Bonifacino JS (2002) A tubular EHD1-containing compartment involved in the recycling of major histocompatibility complex class I molecules to the plasma membrane. EMBO J 21:2557–2567PubMedCrossRefGoogle Scholar
  6. 6.
    Cappai R, Mok SS, Galatis D, Tucker DF, Henry A, Beyreuther K, Small DH, Masters CL (1999) Recombinant human amyloid precursor-like protein 2 (APLP2) expressed in the yeast Pichia pastoris can stimulate neurite outgrowth. FEBS Lett 442:95–98PubMedCrossRefGoogle Scholar
  7. 7.
    Carreno BM, Hansen TH (1994) Exogenous peptide ligand influences the expression and half-life of free HLA class I heavy chains ubiquitously detected at the cell surface. Eur J Immunol 24:1285–1292PubMedCrossRefGoogle Scholar
  8. 8.
    Casanova JE, Wang X, Kumar R, Bhartur SG, Navarre J, Woodrum JE, Altschuler Y, Ray GS, Goldenring JR (1999) Association of Rab25 and Rab11a with the apical recycling system of polarized Madin–Darby canine kidney cells. Mol Biol Cell 10:47–61PubMedGoogle Scholar
  9. 9.
    Cerutti A, Zan H, Schaffer A, Bergsagel L, Harindranath N, Max EE, Casali P (1998) CD40 ligand and appropriate cytokines induce switching to IgG, IgA, and IgE and coordinated germinal center and plasmacytoid phenotypic differentiation in a human monoclonal IgM + IgD + B cell line. J Immunol 160:2145–2157PubMedGoogle Scholar
  10. 10.
    Covell DG, Wallqvist A, Rabow AA, Thanki N (2003) Molecular classification of cancer: unsupervised self-organizing map analysis of gene expression microarray data. Mol Cancer Therap 2:317–332Google Scholar
  11. 11.
    Dasgupta JD, Watkins S, Slayter H, Yunis EJ (1988) Receptor-like nature of class I HLA: endocytosis via coated pits. J Immunol 141:2577–2580PubMedGoogle Scholar
  12. 12.
    Epstein AL, Levy R, Kim H, Henle W, Henle G, Kaplan HS (1978) Biology of the human malignant lymphomas IV: functional characterization of ten diffuse histiocytic lymphoma cell lines. Cancer 42:2379–2391PubMedCrossRefGoogle Scholar
  13. 13.
    Feuerbach D, Burgert H-G (1993) Novel proteins associated with MHC class I antigens in cells expressing adenovirus protein E3/19K. EMBO J 12:3153–3161PubMedGoogle Scholar
  14. 14.
    Foung SKH, Taidi B, Ness D, Grumet FC (1986) A monoclonal antibody against HLA-A11 and A24. Human Immunol 15:316–319CrossRefGoogle Scholar
  15. 15.
    Gorvel JP, Chavrier P, Zerial M, Gruenberg J (1991) Rab5 controls early endosome fusion in vitro. Cell 64:915–925PubMedCrossRefGoogle Scholar
  16. 16.
    Guo J, Thinakaran G, Guo Y, Sisodia SS, Yu FX (1998) A role for amyloid precursor-like protein 2 in corneal epithelial wound healing. Invest Ophthalmol Vis Sci 39:292–300PubMedGoogle Scholar
  17. 17.
    Hunyady L, Baukal AJ, Gaborik Z, Olivares-Reyes JA, Bor M, Szaszak M, Lodge R, Catt KJ, Balla T (2002) Differential PI 3-kinase dependence of early and late phases of recycling of the internalized AT1 angiotensin receptor. J Cell Biol 157:1211–1222PubMedCrossRefGoogle Scholar
  18. 18.
    Iwamura T, Katsuki T, Ide K (1987) Establishment and characterization of a human pancreatic cancer cell line (SUIT-2) producing carcinoembryonic antigen and carbohydrate antigen 19-9. Jpn J Cancer Res 78:54–62PubMedGoogle Scholar
  19. 19.
    Ladasky JJ, Shum BP, Canavez F, Seuanez HN, Parham P (1999) Residue 3 of beta2-microglobulin affects binding of class I MHC molecules by the W6/32 antibody. Immunogenetics 49:312–320PubMedCrossRefGoogle Scholar
  20. 20.
    Li XF, Thinakaran G, Sisodia SS, Yu FS (1999) Amyloid precursor-like protein 2 promotes cell migration toward fibronectin and collagen IV. J Biol Chem 274:27249–27256PubMedCrossRefGoogle Scholar
  21. 21.
    Lopez-Albaitero A, Navak JV, Ogino T, Machandia A, Gooding W, DeLeo AB, Ferrone S, Ferris RL (2006) Role of antigen-processing machinery in the in vitro resistance of squamous cell carcinoma of the head and neck cells to recognition by CTL. J Immunol 176:3402–3409PubMedGoogle Scholar
  22. 22.
    Martinez-Ramirez A, Rodriguez-Perales S, Melendez B, Martinez-Delgado B, Urioste M, Cigudosa JC, Benitez J (2003) Characterization of the A673 cell line (Ewing tumor) by molecular cytogenetic techniques. Cancer Genet Cytogenet 141:138–142PubMedCrossRefGoogle Scholar
  23. 23.
    Miyahara Y, Naota H, Wang L, Hiasa A, Goto M, Watanabe M, Kitano S, Okumura S, Takemitsu T, Yuta A, Majima Y, Lemonnier FA, Boon T, Shiku H (2005) Determination of cellularly processed HLA-A2402-restricted novel CTL epitopes derived from two cancer germ line genes, MAGE-A4 and SAGE. Clin Cancer Res 11:5581–5589PubMedCrossRefGoogle Scholar
  24. 24.
    Morris CR, Petersen JL, Vargas SE, Turnquist HR, McIlhaney MM, Sanderson SD, Bruder JT, Yu YYL, Burgert H-G, Solheim JC (2003) The amyloid precursor-like protein 2 and the adenoviral E3/19K protein both bind to a conformational site on H-2Kd and regulate H-2Kd expression. J Biol Chem 278:12618–12623PubMedCrossRefGoogle Scholar
  25. 25.
    Mu FT, Callaghan JM, Steele-Mortimer O, Stenmark H, Parton RG, Campbell PL, McCluskey J, Yeo JP, Tock EP, Toh BH (1995) EEA1, an early endosome-associated protein: EEA1 is a conserved alpha-helical peripheral membrane protein flanked by cysteine “finger” and contains a calmodulin-binding IQ motif. J Biol Chem 270:133503–133511Google Scholar
  26. 26.
    Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J (1982) Growth of human hepatoma cell lines with differentiated functions in chemically defined medium. Cancer Res 42:3858–3863PubMedGoogle Scholar
  27. 27.
    Naslavsky N, Boehm M, Backlund PS Jr, Caplan S (2004) Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane. Mol Biol Cell 15:2410–2422PubMedCrossRefGoogle Scholar
  28. 28.
    Owens RB, Smith HS, Nelson-Rees WA, Springer EL (1976) Epithelial cell cultures from normal and cancerous human tissues. J Natl Cancer Inst 56:843–849PubMedGoogle Scholar
  29. 29.
    Parham P, Barnstable CJ, Bodmer WF (1979) Use of a monoclonal antibody (W6/32) in structural studies of HLA-A, B, C antigens. J Immunol 123:342–349PubMedGoogle Scholar
  30. 30.
    Parham P, Brodsky FM (1981) Partial purification and some properties of BB7.2: a cytotoxic monoclonal antibody with specificity for HLA-A2 and a variant of HLA-A28Google Scholar
  31. 31.
    Radhakrishna H, Donaldson JG (1997) ADP-ribosylation factor 6 regulates a novel plasma membrane recycling pathway. J Cell Biol 139:49–61PubMedCrossRefGoogle Scholar
  32. 32.
    Rassoulzadegan M, Yang Y, Cuzin F (1998) APLP2, a member of the Alzheimer precursor protein family, is required for correct genomic segregation in dividing mouse cells. EMBO J 17:4647–4656PubMedCrossRefGoogle Scholar
  33. 33.
    Reid PA, Watts C (1990) Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments. Nature 346:655–657PubMedCrossRefGoogle Scholar
  34. 34.
    Ren M, Xu G, Zeng J, De Lemos-Chiarandini C, Adesnik M, Sabatini DD (1998) Hydrolysis of GTP on rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes. Proc Natl Acad Sci USA 95:6187–6192PubMedCrossRefGoogle Scholar
  35. 35.
    Scheinfeld MH, Ghersi E, Laky K, Fowlkes BJ, D’Adamio L (2002) Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription. J Biol Chem 277:44195–44201PubMedCrossRefGoogle Scholar
  36. 36.
    Scherer WF, Syverton JT, Gey GO (1953) Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med 97:695–710PubMedCrossRefGoogle Scholar
  37. 37.
    Seliger B, Ritz U, Ferrone S (2006) Molecular mechanisms of HLA class I antigen abnormalities following viral infection and transformation. Int J Cancer 118:129–138PubMedCrossRefGoogle Scholar
  38. 38.
    Sernee MF, Ploegh HL, Schust DJ (1998) Why certain antibodies cross-react with HLA-A and HLA-G: epitope mapping of two common MHC class I reagents. Mol Immunol 35:177–188PubMedCrossRefGoogle Scholar
  39. 39.
    Sester M, Feuerbach D, Frank R, Preckel T, Gutermann A, Burgert H-G (2000) The amyloid precursor-like protein 2 associates with the major histocompatibility complex class I molecule Kd. J Biol Chem 275:3645–3654PubMedCrossRefGoogle Scholar
  40. 40.
    Sharma M, Naslavsky N, Caplan S (2008) A role for EHD4 in the regulation of early endosomal transport. Traffic, epubGoogle Scholar
  41. 41.
    Shimizu Y, Geraghty DE, Koller BH, Orr HT, DeMars R (1988) Transfer and expression of three cloned human non-HLA-A, B, C class I major histocompatibility complex genes in mutant lymphoblastoid cells. Proc Natl Acad Sci USA 85:227–231PubMedCrossRefGoogle Scholar
  42. 42.
    Shimizu Y, DeMars R (1989) Production of human cells expressing individual transferred HLA-A,-B,-C genes using an HLA-A,-B,-C null human cell line. J Immunol 142:3320–3328PubMedGoogle Scholar
  43. 43.
    Slunt HH, Thinakaran G, Von Koch C, Lo ACY, Tanzi RE, Sisodia SS (1994) Expression of a ubiquitous, cross-reactive homologue of the mouse β-amyloid precursor protein. J Biol Chem 269:2637–2644PubMedGoogle Scholar
  44. 44.
    Soule HD, Vazquez J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1416PubMedGoogle Scholar
  45. 45.
    Stam N, Spits H, Ploegh H (1986) Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol 137:2299–2306PubMedGoogle Scholar
  46. 46.
    Stam NJ, Vroom TM, Peters PJ, Pastoors EB, Ploegh HL (1990) HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. Int Immunol 2:113–125PubMedCrossRefGoogle Scholar
  47. 47.
    Stenmark H, Parton RG, Steele-Mortimer O, Lutcke A, Gruenberg J, Zerial M (1994) Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis. EMBO J 13:1287–1296PubMedGoogle Scholar
  48. 48.
    Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF (1978) Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer 21:274–281PubMedCrossRefGoogle Scholar
  49. 49.
    Thinakaran G, Kitt CA, Roskams AJ, Slunt HH, Masliah E, von Koch C, Ginsberg SD, Ronnett GV, Reed RR, Price DL (1995) Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. J Neurosci 15:6314–6326PubMedGoogle Scholar
  50. 50.
    Tsutsumida H, Swanson BJ, Singh PK, Caffrey TC, Kitajima S, Goto M, Yonezawa S, Hollingsworth MA (2006) RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells. Clin Cancer Res 12:2976–2987PubMedCrossRefGoogle Scholar
  51. 51.
    Tuli A, Sharma M, Wang X, Naslavsky N, Caplan S, Solheim JC (2008) Specificity of amyloid precursor-like protein 2 interactions with MHC class I molecules. Immunogenetics 60:303–313PubMedCrossRefGoogle Scholar
  52. 52.
    Tuli A, Sharma M, McIlhaney MM, Talmadge JE, Naslavsky N, Caplan S, Solheim JC (2008) Amyloid precursor-like protein 2 increases the endocytosis, instability, and turnover of the H2-Kd MHC class I molecule. J Immunol 181:1978–1987PubMedGoogle Scholar
  53. 53.
    Turnquist HR, Solheim JC (2001) Analysis of MHC class I interactions with endoplasmic reticulum proteins. Methods Mol Biol 156:165–173PubMedGoogle Scholar
  54. 54.
    Walsh DM, Fadeeva JV, Lavoie MJ, Paliga K, Egger S, Kimberly WT, Wasco W, Selkoe DJ (2003) Gamma-secretase cleavage and binding to FE65 regulate the nuclear translocation of the intracellular C-terminal domain (ICD) of the APP family of proteins. Biochemistry 42:6664–6673PubMedCrossRefGoogle Scholar
  55. 55.
    Walsh DM, Minogue AM, Frigerio CS, Fadeeva JV, Wasco W, Selkoe DJ (2007) The APP family of proteins: similarities and differences. Biochem Soc Trans 5:416–420Google Scholar
  56. 56.
    Wang B, Yang L, Wang Z, Zheng H (2007) Amyloid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc Natl Acad Sci USA 104:14140–14145PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Amit Tuli
    • 1
    • 2
  • Mahak Sharma
    • 2
  • Xiaojian Wang
    • 1
  • Laura C. Simone
    • 1
  • Haley L. Capek
    • 1
  • Steven Cate
    • 3
  • William H. Hildebrand
    • 3
  • Naava Naslavsky
    • 2
  • Steve Caplan
    • 2
  • Joyce C. Solheim
    • 1
    • 2
  1. 1.Eppley Institute for Research in Cancer and Allied DiseasesUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Department of Microbiology and ImmunologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

Personalised recommendations