Fm. Brichory et al., An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer, P NAS US, 98(17), 2001, pp. 9824-9829
Citations number
42
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The identification of circulating tumor antigens or their related autoantib
odies provides a means for early cancer diagnosis as well as leads for ther
apy. The purpose of this study was to identify proteins that commonly induc
e a humoral response in lung cancer by using a proteomic approach and to in
vestigate biological processes that may be associated with the development
of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcin
oma cell line (A549) and from lung tumors were subjected to two-dimensional
PAGE, followed by Western blot analysis in which individual sera were test
ed for primary antibodies. Sera from 54 newly diagnosed patients with lung
cancer and 60 patients with other cancers and from 61 noncancer controls we
re analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of
patients with squamous cell lung carcinoma but none of the noncancer contro
ls exhibited IgG-based reactivity against proteins identified as glycosylat
ed annexins I and/or II. Immunohistochemical analysis showed that annexin I
was expressed diffusely in neoplastic cells in lung tumor tissues, whereas
annexin II was predominant at the cell surface. Interestingly, IL-6 levels
were significantly higher in sera of antibody-positive lung cancer patient
s compared with antibody-negative patients and controls. We conclude that a
n immune response manifested by annexins I and II autoantibodies occurs com
monly in lung cancer and is associated with high circulating levels of an i
nflammatory cytokine. The proteomic approach we have implemented has utilit
y for the development of serum-based assays for cancer diagnosis as we repo
rt in this paper on the discovery of antiannexins I and/or II in sera from
patients with lung cancer.