An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

Abstract

The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and͞or 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 patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and͞or II in sera from patients with lung cancer.

Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression

“…Supporting the role of annexins in tumorigenesis, some immunohistochemical studies in lung cancer indicated that other annexin members were expressed diffusedly in neoplastic cells. 26 Our identification of upregulated SPRR1, S100A9, ANXA1 and ANXA8 in SC is consistent with the epidermal nature of SC, further strengthening the validity of our microarray results.…”

Immunoproteomic identification of bovine pericardium xenoantigens

“…Interestingly, some of the proteins identified as antigens in this study have been previously identified as antigenic in other settings, and, in each case, their antigenic domains have been mapped to protein sites [47,[51][52][53]. Furthermore, 15 of the putative antigens were identified from multiple closely associated spots, suggesting that varying degrees of PTM were present, but that antigenicity was not dependent on PTM [44,45,47,49]. Additional studies will be necessary to both confirm xenogeneic antigenicity and identify the specific antigenic domain of each identified putative xenoantigen.…”

“…This approach led to the identification of 31 putative antigenic proteins capable of eliciting a T cell-dependent antibody response, as revealed by IgG production [42,43]. Similar approaches have been used recently to identify relevant antigenic proteins in oncologic, autoimmune, and infectious diseases [44][45][46][47][48][49][50]. To our knowledge, this study is the first to apply an immunoproteomic approach to identify potential antigens in xenotransplanted tissues.…”

Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways

“…Many of these genes have not been previously associated with paclitaxel-induced apoptosis and hence are worth further study. Increased serum levels of IL-6 in patients with lung cancer were proposed as reflection of an immune response of cancer patients (healthy subjects 23.1471.88 pg/ml; lung cancer patients 60.5376.27 pg/ ml, P ¼ 0.003) (Brichory et al, 2001). However, in the absence of immune cells, we identified the 24-h secretion amounts of IL-6 in 87.5% of eight ovarian cancer cell lines to be from 4 to 1625 pg/1000 cells (mean ¼ 482, median ¼ 130 pg/1000 cells) (Figure 4b).…”