Role of the tumour necrosis family ligand APRIL in solid tumour development: Retrospective studies in bladder, ovarian and head and neck carcinomas

doi:10.1016/j.ejca.2008.07.007

European Journal of Cancer

Volume 44, Issue 15, October 2008, Pages 2097-2100

https://doi.org/10.1016/j.ejca.2008.07.007 Get rights and content

Abstract

A proliferation inducing ligand (APRIL) from the tumour necrosis family (TNF) promotes the natural development of solid tumours in pre-clinical models. Here, we studied the role of APRIL in patients with urothelial bladder, epithelial surface ovarian, and head and neck squamous carcinomas. By using immunohistochemistry, we revealed an upregulation of APRIL expression in lesions from a significant subset of patients compared to corresponding healthy tissues. APRIL upregulation was not due to autocrine production by tumour cells, but rather originated from infiltration of APRIL-producing neutrophils. Heparan sulphate proteoglycan (HSPG) efficiently concentrated secreted APRIL in lesions. Despite this retention, in situ APRIL upregulation did not significantly alter disease-free and overall survivals of carcinoma patients in retrospective studies. This indicates that APRIL is not potent enough to promote the development of solid tumour cells under the pressure of chemotherapy.

Introduction

A proliferation inducing ligand (APRIL, TNFSF13) from the tumour necrosis family (TNF) was originally found in cell lines and primary samples from various tumour lesions.¹ APRIL mediates a survival/proliferation signal to lymphoma cells, own to their expression of the APRIL-signalling receptors, the transmembrane activator, calcium modulator and cyclophilin ligand interactor (TACI, TNFRSF13) and the B-cell maturation antigen (BCMA, TNFRSF17).² This lymphoma-promoting role was recently substantiated clinically with a worst prognosis for patients harbouring high level of APRIL expression in chronic lymphocytic leukaemia³ and diffuse large B-cell lymphoma.⁴

APRIL has also been implicated in the promotion of solid tumour development in in vitro and in vivo pre-clinical models.5, 6, 7 At first, this promoting role for APRIL on solid tumour cells was not well understood, since TACI and BCMA expression is restricted to hematopoietic cells.⁸ Recently, heparan sulphate side chains of proteoglycans (HSPG) were identified as APRIL-binding partners,9, 10 demonstrating the presence of an APRIL receptor on solid tumour cells with multiple roles in tumourigenesis.¹¹ Here, we present the first retrospective clinical study on the role of APRIL in carcinoma patients receiving standard chemotherapy. We selected widely different solid tumour types such as urothelial bladder, surface epithelial ovarian and head and neck squamous cell carcinomas to broaden our study.

Section snippets

Patients and methods

Patients, treatments and tumour characteristics are summarised in Table 1S. Projects were all reviewed and approved by Local Ethics Committees. Patients with a first time diagnosis of carcinoma were included in the study. All tumours were reviewed prior to analyses to confirm histological grade and stage. We performed immunohistochemistry with a pair of APRIL-specific antibodies, Stalk-1 and Aprily-2, on tumour micro-arrays as previously described.⁴ Aprily-2 immunoexpression was scored [0] when

Results and discussion

We performed immunohistochemistry study for APRIL on tumour micro-arrays from patients with bladder (n = 67), ovarian (n = 211) and head and neck (n = 128) carcinomas with a pair of APRIL-specific antibodies selectively identifying cells producing APRIL (Stalk-1 reactivity) and secreted APRIL (Aprily-2 reactivity).⁴ We observed 52%, 51% and 53% of APRIL^high lesions in bladder, ovary and head and neck carcinomas, respectively, with the Stalk-1 antibody. With the Aprily-2 antibody, results were very

Conflict of interest statement

None declared.

Acknowledgements

This work was supported by the Docteur Henri Dubois Ferrière/Dinu Lipatti Foundation, the Leenaards foundation and the Swiss National Science Foundation.

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Human B lymphocyte malignancies: exploitation of BLyS and APRIL and their receptors
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There are more references available in the full text version of this article.

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Short CommunicationRole of the tumour necrosis family ligand APRIL in solid tumour development: Retrospective studies in bladder, ovarian and head and neck carcinomas

Abstract

Introduction

Section snippets

Patients and methods

Results and discussion

Conflict of interest statement

Acknowledgements

Blood

BAFF AND APRIL: a tutorial on B cell survival

Annu Rev Immunol

Human B lymphocyte malignancies: exploitation of BLyS and APRIL and their receptors

Curr Dir Autoimmun

APRIL but not BLyS serum levels are increased in chronic lymphocytic leukemia: prognostic relevance of APRIL for survival

Haematologica

APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth

J Exp Med

A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth

J Exp Med

APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis

Cell Death Differ

Short Communication
Role of the tumour necrosis family ligand APRIL in solid tumour development: Retrospective studies in bladder, ovarian and head and neck carcinomas