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Sperm-associated antigen 1 is expressed early in pancreatic tumorigenesis and promotes motility of cancer cells

Oncogene volume 26, pages 1533–1545 (2007)Cite this article

Abstract

Sperm-associated antigen 1 (SPAG1) was recently identified in a rare form of infertility where anti-SPAG1 antibodies derived from the serum of an infertile woman were reported to cause sperm agglutination. Except for its expression and potential role in spermatogenesis, the function of SPAG1 is completely unknown. The unexpected finding of high levels of SPAG1 expression in pancreatic adenocarcinoma compared to normal pancreatic tissue in our previous cDNA array experiments prompted us to look in more detail at the expression and role of this gene in a panel of normal and malignant human tissues as well as in a larger series of pancreatic cancer specimens. We have generated an SPAG1-specific monoclonal antibody and showed high levels of SPAG1 protein in testis and in a large proportion of pancreatic ductal adenocarcinomas (PDAC). In the latter, SPAG1 expression was predominantly cytoplasmic and confined to malignant cells. Furthermore, the extent and intensity of SPAG1 expression was shown to be associated with stage and tumour nodal status, while analysis of precursor lesions, pancreatic intraepithelial neoplasias (PanINs), demonstrated its increased immunoreactivity with increasing PanIN grade, suggesting that SPAG1 is a novel marker of PDAC progression. Immunocytochemical analysis demonstrated colocalization of SPAG1 with microtubules, and their association was confirmed by co-immunoprecipitation; subsequent motility assays further substantiated a potential role of SPAG1 in cancer cell motility. Combined with the finding of its early expression in PDAC development, our data suggest that SPAG1 could contribute to the early spread and poor prognosis of pancreatic adenocarcinoma.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

SPAG1:

sperm-associated antigen 1

PanIN:

pancreatic intraepithelial neoplasia

PDAC:

pancreatic ductal adenocarcinoma

CP:

chronic pancreatitis

TPR motif:

tetratricopeptide motif

QRT–PCR:

quantitative real-time reverse transcription–polymerase chain reaction

ESI, electrospray ionization:

CT genes' cancer/testis genes

IHC:

immunohistochemistry

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Acknowledgements

We thank Dr David Snary (Applied Development Laboratory, CRT) for assistance in selecting the peptide epitopes and Ms Maggie Stubbs for generating monoclonal SPAG1 antibody; Dr Wang (Institute of Basic Medical Sciences, Beijing, China) for anti-SPAG1 polyclonal antibody; Professor Holger Kalthoff (University of Kiel, Germany) for serum samples; Dr Kit-Yi Leung (Clinical Pharmacology) for help with MS and Ms Catherine Okello (Thames Cancer Registry) for providing the missing patient information. This work was supported by Cancer Research UK, Mike Stone Cancer Research Fund and Graduate College 460 grant, University of Ulm, Germany (AN).

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Author notes

  1. A Neesse and R Gangeswaran: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Research UK Molecular Oncology Unit, Barts and the London School of Medicine and Dentistry, Queen Mary's University, John Vane Science Building, Charterhouse Square, London, UK

    A Neesse, R Gangeswaran, M E Weeks, N R Lemoine & T Crnogorac-Jurcevic

  2. Department of Pathology, Klinikum Saarbrücken, Saarbrücken, Germany

    J Luettges

  3. Department of Histopathology, The Royal London Hospital, Whitechapel, London, UK

    R Feakins

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  1. A Neesse
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  7. T Crnogorac-Jurcevic
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Corresponding author

Correspondence to T Crnogorac-Jurcevic.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Neesse, A., Gangeswaran, R., Luettges, J. et al. Sperm-associated antigen 1 is expressed early in pancreatic tumorigenesis and promotes motility of cancer cells. Oncogene 26, 1533–1545 (2007). https://doi.org/10.1038/sj.onc.1209961

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