Skip to main content
SpringerLink
Log in
Book cover

Isolation and Molecular Characterization of Circulating Tumor Cells pp 275–284Cite as

Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 994))

Abstract

We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients’ blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abd Hamid UM, Royle L, Saldova R et al (2008) A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression. Glycobiology 18(12):1105–1118

    Article  CAS  PubMed  Google Scholar 

  • Anders CK, Carey LA (2009) Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer. Clin Breast Cancer 9(Suppl 2):S73–S81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Apostolopoulos V, Pietersz GA, Tsibanis A et al (2006) Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]. Breast Cancer Ress: BCR 8(3):R27

    Article  Google Scholar 

  • Brenton JD, Carey LA, Ahmed AA et al (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol Off J Am Soc Clin Oncol 23(29):7350–7360

    Article  CAS  Google Scholar 

  • Chatterjee SK, Zetter BR (2005) Cancer biomarkers: knowing the present and predicting the future. Future Oncol 1(1):37–50

    Article  CAS  PubMed  Google Scholar 

  • Codington JF, Sanford BH, Jeanloz RW (1972) Glycoprotein coat of the TA3 cell. Isolation and partial characterization of a sialic acid containing glycoprotein fraction. Biochemistry 11(14):2559–2564

    Article  CAS  PubMed  Google Scholar 

  • Codington JF, Mass N, Haavik S et al (1997) Antibodies to human carcinoma antigen. US Pat No 5,693,763, Dec 2, 1997

    Google Scholar 

  • Codington JF, Haavik S, Nikrui N et al (2002) Immunologic quantitation of the carcinoma specific human carcinoma antigen in clinical samples. Cancer 94(3):803–813

    Article  CAS  PubMed  Google Scholar 

  • Das M, Riess JW, Frankel P et al (2012) ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy. Lung Cancer 77(2):421–426

    Article  PubMed  Google Scholar 

  • Dube DH, Bertozzi CR (2005) Glycans in cancer and inflammation – potential for therapeutics and diagnostics. Nat Rev Drug Discov 4(6):477–488

    Article  CAS  PubMed  Google Scholar 

  • Feizi T, Kabat EA, Vicari G et al (1971a) Immunochemical studies on blood groups. XLVII. The I antigen complex – precursors in the A, B, H, Lea, and leb blood group system – hemagglutination-inhibition studies. J Exp Med 133(1):39–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feizi T, Kabat EA, Vicari G et al (1971b) Immunochemical studies on blood groups.XLIX. The I antigen complex: specificity differences among anti-I sera revealed by quantitative precipitin studies; partial structure of the I determinant specific for one anti-I serum. J Immunol 106(6):1578–1592

    CAS  PubMed  Google Scholar 

  • Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56(10):2237–2244

    CAS  PubMed  Google Scholar 

  • Gao C, Liu Y, Zhang H et al (2014) Carbohydrate sequence of the prostate cancer-associated antigen F77 assigned by a mucin O-glycome designer Array. J Biol Chem 289(23):16462–16477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haidopoulos D, Konstadoulakis MM, Antonakis PT et al (2000) Circulating anti-CEA antibodies in the sera of patients with breast cancer. Eur J Surg Oncol: J Eur Soc Surg Oncol Br Assoc Surg Oncol 26(8):742–746

    Article  CAS  Google Scholar 

  • Hakomori S (1989) Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens. Adv Cancer Res 52:257–331

    Article  CAS  PubMed  Google Scholar 

  • Hakomori S (2001) Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines. Adv Exp Med Biol 491:369–402

    Article  CAS  PubMed  Google Scholar 

  • Hayashi N, Yamauchi H (2012) Role of circulating tumor cells and disseminated tumor cells in primary breast cancer. Breast Cancer 19(2):110–117

    Article  PubMed  Google Scholar 

  • Jacob K, Sollier C, Jabado N (2007) Circulating tumor cells: detection, molecular profiling and future prospects. Expert Rev Proteomics 4(6):741–756

    Article  CAS  PubMed  Google Scholar 

  • Kabat EA (1956) Blood group substances, their chemistry and immunochemistry. Academic, New York

    Google Scholar 

  • Li R, Yao JL, Bourne PA et al (2004) Frequent expression of human carcinoma-associated antigen, a mucin-type glycoprotein, in cells of prostatic carcinoma. Arch Pathol Lab Med 128(12):1412–1417

    CAS  PubMed  Google Scholar 

  • Liang S, Yao J, Bourne PA et al (2004) Overexpression of human carcinoma-associated antigen in esophageal adenocarcinoma and its precursor lesions. Am J Clin Pathol 122(5):747–751

    Article  PubMed  Google Scholar 

  • Liu X, Hsieh HB, Campana D et al (2012) A new method for high speed, sensitive detection of minimal residual disease. Cytometry Part A J Int Soc Anal Cytol 81(2):169–175

    Article  Google Scholar 

  • Nakagoe T, Fukushima K, Itoyanagi N et al (2002) Expression of ABH/Lewis-related antigens as prognostic factors in patients with breast cancer. J Cancer Res Clin Oncol 128(5):257–264

    Article  CAS  PubMed  Google Scholar 

  • Newsom-Davis TE, Wang D, Steinman L et al (2009) Enhanced immune recognition of cryptic glycan markers in human tumors. Cancer Res 69(5):2018–2025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nonaka M, Fukuda MN, Gao C et al (2014) Determination of carbohydrate structure recognized by prostate-specific F77 monoclonal antibody through expression analysis of Glycosyltransferase genes. J Biol Chem 289(23):16478–16486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Persson J, Backstrom M, Johansson H et al (2009) Molecular evolution of specific human antibody against MUC1 mucin results in improved recognition of the antigen on tumor cells. Tumour Biol J Int Soc Oncodev Biol Med 30(4):221–231

    Article  CAS  Google Scholar 

  • Renkonen J, Paavonen T, Renkonen R (1997) Endothelial and epithelial expression of sialyl Lewisx and sialyl Lewisa in lesions of breast carcinoma. Int J Cancer 74(3):296–300

    Article  CAS  PubMed  Google Scholar 

  • Shibata S, Raubitschek A, Leong L et al (2009) A phase I study of a combination of yttrium-90-labeled anti-carcinoembryonic antigen (CEA) antibody and gemcitabine in patients with CEA-producing advanced malignancies. Clin Cancer Res Off J Am Assoc Cancer Res 15(8):2935–2941

    Article  CAS  Google Scholar 

  • Somlo G, Lau SK, Frankel P et al (2011) Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology. Breast Cancer Res Treat 128(1):155–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomlinson IP, Whyman A, Barrett JA et al (1995) Tumour marker CA15-3: possible uses in the routine management of breast cancer. Eur J Cancer 31A(6):899–902

    Article  CAS  PubMed  Google Scholar 

  • Vassilaros S, Tsibanis A, Tsikkinis A et al (2013) Up to 15-year clinical follow-up of a pilot phase III immunotherapy study in stage II breast cancer patients using oxidized mannan-MUC1. Immunotherapy 5(11):1177–1182

    Article  CAS  PubMed  Google Scholar 

  • Vicari G, Kabat EA (1970) Structures and activities of oligosaccharides produced by alkaline degradation of a blood group substance lacking A, B, H, Le b specificities. Biochemistry 9(17):3414–3421

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Liu X, Hsieh B et al (2015a) Exploring glycan markers for immunotyping and precision-targeting of breast circulating tumor cells. Arch Med Res 46(8):642–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D, Tang J, Liu S et al (2015b) Blood group precursor cryptic glyco-epitopes as breast cancer cell surface markers for immune recognition and targeting. J Immunol Res 9:510810

    Google Scholar 

  • Wu AM, Khoo KH, Yu SY et al (2007) Glycomic mapping of pseudomucinous human ovarian cyst glycoproteins: identification of Lewis and sialyl Lewis glycotopes. Proteomics 7(20):3699–3717

    Article  CAS  PubMed  Google Scholar 

  • Yao JL, Bourne PA, Yang Q et al (2004) Overexpression of human carcinoma-associated antigen in urothelial carcinoma of the bladder. Arch Pathol Lab Med 128(7):785–787

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the Kabat Collection of Carbohydrate Antigens at SRI International for a number of carbohydrate antigens that were applied in this study.

This work was supported in part by NIH grants U01CA128416 (DW) and R56AI118464 (DW), and by SRI International IR&D funds (DW and XL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of Interest

There are no conflicts of interest to declare for any of the authors involved in this work.

Author information

Authors and Affiliations

  1. Tumor Glycomics Laboratory, Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA, 94025-3493, USA

    Denong Wang & Lisa Wu

  2. Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA, 94025-3493, USA

    Xiaohe Liu

Authors
  1. Denong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaohe Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Denong Wang .

Editor information

Editors and Affiliations

  1. University of California San Francisco, San Francisco, California, USA

    Mark Jesus M. Magbanua

  2. University of California San Francisco, San Francisco, California, USA

    John W. Park

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Wang, D., Wu, L., Liu, X. (2017). Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells. In: Magbanua, M., Park, J. (eds) Isolation and Molecular Characterization of Circulating Tumor Cells. Advances in Experimental Medicine and Biology, vol 994. Springer, Cham. https://doi.org/10.1007/978-3-319-55947-6_15

Download citation

Publish with us

Policies and ethics

Search

Navigation