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A comparative analysis of oncofetal fibronectin and tenascin-C incorporation in tumour vessels using human recombinant SIP format antibodies

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Abstract

Tumour angioneogenesis is associated with the reexpression of oncofetal fibronectin (oncFn) and tenascin-C (oncTn-C) splice variants, which may serve as targets for antibody-based pharmacodelivery. Knowledge of the vascular distribution and organization in different tumours is of importance for the understanding of tumour vessel formation and might be crucial for therapy. Therefore, human SIP format antibodies against Fn ED-A, Fn ED-B and Tn-C A and C splice domains were used for immunofluorescence labelling in renal, lung, oral, colon, breast and urinary bladder carcinoma specimens and in a renal carcinoma xenograft. The spatial relation to stroma, vessels and vascular basement membrane (vBM) was analysed including CD31 and laminin α4 chain antibodies. Renal cell carcinomas and atypical carcinoid of the lung revealed vessel-restricted oncFn and/or oncTn-C depositions; all other entities showed a variable stroma positivity including vessels. The individual pattern of oncFn/oncTn-C incorporation in the vBM depended on tumour type, vessel size and intratumoural heterogeneity. There was a stratification of the vessel wall showing luminal oncFn and extraluminal oncTn-C depositions. As shown in the xenograft, perivascular oncTn-C is provided by carcinoma cells. In conclusion, tumours differ in the pattern of Fn or Tn-C isoform positivity in the vessel wall, potentially representing a tumour type specific endothelial cell–tumour cell–stromal cell interaction. Carcinoma cells themselves are involved in vascular Tn-C matrix organization. Up to antigen distribution, Fn and Tn-C domain antibodies may serve as vehicles for antiangiogenetic and antifibrotic agents; oncFn/oncTn-C based targeting should be adapted individually.

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Acknowledgments

The authors are grateful to Professor Ismo Virtanen for providing the anti-laminin α4 chain antibody FC10. Furthermore, the authors would like to thank Claudia Seliger for the excellent technical assistance. The research leading to the results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. Health-F2-2008-201342 (ADAMANT).

Conflict of interest statement

Dario Neri is a co-founder and shareholder of Philogen, the company which owns the rights of the F8, L19, F16 and G11 antibodies.

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Authors and Affiliations

  1. Institute of Pathology, University Hospital Jena, Ziegelmühlenweg 1, 07743, Jena, Germany

    Alexander Berndt, Robert Köllner & Petra Richter

  2. Department of Internal Medicine I, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany

    Marcus Franz

  3. Department of Pediatrics, University Hospital Jena, Kochstraße 2, 07743, Jena, Germany

    Astrid Voigt

  4. Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institute, Naumburger Straße 96a, 07743, Jena, Germany

    Angela Berndt

  5. Laboratory of Cell Biology, Istituto Nazionale per la Ricerca sul Cancro, Largo Benzi Rosanna 10, 16132, Genoa, Italy

    Laura Borsi

  6. Mario Negri Institute for Pharmacological Research, Via La Masa 19, 20156, Milan, Italy

    Raffaella Giavazzi

  7. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland

    Dario Neri

  8. Institute of Pathology, HELIOS-Klinikum Erfurt, Nordhäuser Straße 74, 99089, Erfurt, Germany

    Hartwig Kosmehl

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  1. Alexander Berndt
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  2. Robert Köllner
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  3. Petra Richter
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  4. Marcus Franz
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  6. Angela Berndt
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  8. Raffaella Giavazzi
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  9. Dario Neri
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  10. Hartwig Kosmehl
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Correspondence to Alexander Berndt.

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A. Berndt and R. Köllner contributed equally to the study.

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Berndt, A., Köllner, R., Richter, P. et al. A comparative analysis of oncofetal fibronectin and tenascin-C incorporation in tumour vessels using human recombinant SIP format antibodies. Histochem Cell Biol 133, 467–475 (2010). https://doi.org/10.1007/s00418-010-0685-y

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