Widespread expressions of immunoglobulin superfamily proteins in cancer cells
Tóm tắt
RP215 monoclonal antibody (Mab) was shown to recognize a carbohydrate-associated epitope of cancer cell–expressed glycoproteins, known as CA215. Extensive MALDI-TOF MS analysis was performed to search for the molecular identity of CA215. Besides immunoglobulin (Ig) heavy chains, homology to human T-cell receptors (TCR) and Ig-like cell adhesion molecules was also detected. By using RT-PCR and cDNA sequencing, it was observed that as many as 80% of cancer cell lines showed significant levels of gene expressions of TCR-α and TCR-β. Selected Ig-like cell adhesion molecules such as CD47, CD54, CD58 and CD 147 were also highly expressed among all the cell lines tested. In contrast, co-receptors and co-stimulators of TCR such as CD3, CD4 and CD8 were rarely expressed demonstrating the non-functional nature of TCR in cancer cells. Results of immunohistochemical staining and Western blot assays of cancer cell lines as well as cancerous tissue sections were consistent with these observations. Anti-TCR and anti-human IgG antibodies were shown to induce complement-dependent cytotoxicity and apoptosis of cultured cancer cells indicating the surface nature of Ig-like proteins. Based on these experimental observations, it was hypothesized that the expressions of these immunoglobulin superfamily (IgSF) proteins may be relevant to the immune protection and proliferations of cancer cells during carcinogenesis or cancer progression. Surface-bound TCR-like proteins as well as immunoglobulins may be the potential targets for RP215-based anti-cancer drugs.
Tài liệu tham khảo
Lee G, Laflamme E, Chien CH, Ting HH (2008) Molecular identity of a pan cancer marker, CA215. Cancer Bio Ther 7:2007–2014
Lee G, Wu Q, Li CH, Ting HH, Chien CH (2006) Recent studies of a new carbohydrate-associated pan cancer marker, CA215. J Clin Ligand Assay 29:47–51
Lee G, Ge B (2009) Cancer cell expressions of immunoglobulin heavy chains with unique carbohydrate-associated biomarker. Cancer Biomarkers 5:177–188
Lee G, Ge B (2010) Inhibition of in vitro tumor cell growth by RP215 monoclonal antibody and antibodies raised against its anti-idiotype antibodies. Cancer Immunol Immunother 59:1347–1356
Lee G, Chu RA, Ting HH (2009) Preclinical assessment of anti-cancer drugs by using RP215 monoclonal antibody. Cancer Biol Ther 8:161–166
Lee G, Ge B, Huang TK, Zheng G, Duan J, Wang IH (2009) Positive identification of CA215 pan cancer biomarker from serum specimens of cancer patients. Cancer Biomarkers 6:111–117
Band H, Hochstenbach F, Parker CM, McLean J, Krangel MS, Brenner MB (1989) Expression of human T cell receptor-gamma delta structural forms. J Immunol 15:3627–3633
Kieke MC, Shusta EV, Boder ET, Teyton L, Wittrup KD, Kranz DM (1999) Selection of functional T cell receptor mutants from a yeast surface-display library. Proc Natl Acad Sci 11:5651–5656
Janeway CA Jr. et al (2005) Immunobio, 6th ed., Garland Science. ISBN 0-443-07310-4
Kimoto Y (1998) Expression of heavy-chain constant region of immunoglobulin and T-cell receptor gene transcripts in human non-hematopoietic tumor cell lines. Genes Chromosomes Cancer 22:83–86
Harpaz Y, Chothia C (1994) Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. J Mol Biol 13:528–539
Peggs KS, Allison JP (2005) Co-stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily. Br J Haematol 130:809–824
Lee CY, Chen KW, Sheu FS, Tsang A, Chao KC, Ng HT (1992) Studies of a tumor-associated antigen, COX-1, recognized by a monoclonal antibody. Cancer Immunol Immunother 35:19–26
Lee CY, Ho J, Chow SN, Yasojima K, Schwab C, McGeer PL (2000) Immunoidentification of gonadotropin releasing hormone receptor in human sperm, pituitary and cancer cells. Am J Reprod Immunol 44:170–177
Lee G, Ng HT (1995) Clinical evaluations of a new ovarian cancer marker, COX-1. Int J Gynaecol Obstet 49(Suppl):S27–S32
Griffioen M, van Egmond EH, Kester MG, Willemze R, Falkenburg JH, Heemskerk MH (2009) Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy. Haematologica 94:1316–1320
Zhao X, Singh S, Pardoux C, Zhao J, Hsi ED, Abo A, Korver W (2010) Targeting C-type lectin-like molecule-1 for antibody-mediated immunotherapy in acute myeloid leukemia. Haematologica 95:71–78
Filman DJ, Brawn RJ, Dandliker WB (1975) Intracellular supravital stain delocalization as an assay for antibody-dependent complement-mediated cell damage. J Immunol Methods 6:189–207
Yan T, Berry SE, Desai AB, Kinsella TJ (2003) DNA mismatch repair (MMR) mediates 6-thioguanine genotoxicity by introducing single-strand breaks to signal a G2-M arrest in MMR-proficient RKO cells. Clin Cancer Res 9:2327–2334
Balakrishnan K, Krishnan NM, Kulkarni A, Rao BJ (2009) Human Rad51 mediated DNA unwinding is facilitated by conditions that favour Rad51-dsDNA aggregation. BMC Biochem 10:2
Liu AY (2000) Differential expression of cell surface molecules in prostate cancer cells. Cancer Res 1:3429–3434
Liu AY, Peehl DM (2001) Characterization of cultured human prostatic epithelial cells by cluster designation antigen expression. Cell Tissue Res 305:389–397
Liu AY, True LD (2002) Characterization of prostate cell types by CD cell surface molecules. Am J Pathol 160:37–43
Zhang S, Mao Y, Huang J, Ma T, Zhang L, Zhu X, Zheng J, Wu L, Yin CC, Qiu X (2010) Immunoglobulin gene locus events in epithelial cells of lactating mouse mammary glands. Cell Mol Life Sci 67:985–994
Chen Z, Qiu X, Gu J (2009) Immunoglobulin expression in non-lymphoid lineage and neoplastic cells. Am J Pathol 174:1139–1148
Huang J, Zhang L, Ma T, Zhang P, Qiu X (2009) Expression of immunoglobulin gene with classical V-(D)-J rearrangement in mouse testis and epididymis. J Histochem Cytochem 57:339–349
Zhu X, Li C, Sun X, Mao Y, Li G, Liu X, Zhang Y, Qiu X (2008) Immunoglobulin mRNA and protein expression in human oral epithelial tumor cells. Appl Immunohistochem Mol Morphol 16:232–238
Witherden DA, Verdino P, Rieder SE, Garijo O, Mills RE, Teyton L et al (2010) The junctional adhesion molecule JAML is a costimulatory receptor for epithelial gd T cell activation. Science 329:1205–1210
Verdino P, Witherden DA, Havran WL, Wilson IA (2010) The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3K. Science 329:1210–1214
Barclay A (2003) Membrane proteins with immunoglobulin-like domains—a master superfamily of interaction molecules. Semin Immunol 15:215–223
Harpaz Y, Chothia C (1994) Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. J Mol Biol 238:528–539
Lee CYG (2008) Carbohydrate-containing pan cancer marker. US patent application No. 12/599284, WO2008/138139 A1
Lee CYG (2010) Carbohydrate hapten-based anti-cancer vaccines and antibody drugs. US Provisional Patent Application Reference No. 61634-30003.00
Poust J (2008) Targeting metastatic melanoma. Am J Health Syst Pharm 15(65(24 Suppl 9)):S9–S15
Weber J (2007) Review: anti–CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist 12:864–872