Furthermore, the function of ephrin-A1 as a biomarker still remains elusive, and especially in NSCLC further studies are certainly required

Furthermore, the function of ephrin-A1 as a biomarker still remains elusive, and especially in NSCLC further studies are certainly required. Conclusions We have shown that in the present cohort of NSCLC patients S100A4-positive tumors were smaller and more differentiated than tumors without expression. observed in 57% of cases for cytoplasmic S100A4, 46% for nuclear S100A4, 86% for ephrin-A1 and 77% for osteopontin. Interestingly, S100A4 expression was associated with ephrin-A1 also Ro 25-6981 maleate in vivo, but there was no association between S100A4 and osteopontin. Expression levels of S100A4 and ephrin-A1 were significantly higher in adenocarcinomas compared to other histological subtypes, and S100A4-positive tumors were smaller and more differentiated than tumors without expression. Conclusions Our findings suggest that S100A4, ephrin-A1 and osteopontin are involved in the biology of NSCLC, and further investigation of their potential use as biomarkers in NSCLC is usually warranted. Ephrin-A1 is supposed to act as a tumor suppressor through its favored receptor EphA2 [25] which is usually overexpressed in NSCLC [41]Comparable to its ligand, the role of EphA2 in malignancy is usually somewhat conflicting. Increased expression is usually associated with poor clinical outcome in several tumor types, including NSCLC [3,25,42,43]. However, EphA2 can also act as a tumor suppressor [43], and recently, high Rabbit Polyclonal to WEE2 expression of both EphA2 and ephrin-A1 was found to be related to favorable prognostic factors in stage I NSCLC patients [25]. Based on our findings that S100A4 is usually associated with small tumor size and a less aggressive phenotype, one might speculate that S100A4-mediated induction of ephrin-A1 could be implicated in reduced tumor growth and invasiveness in NSCLC. However, ephrin-A1 expression was not associated with tumor size, differentiation or tumor stage, indicating that at least these S100A4-associated features are impartial of ephrin-A1. Overall, these results suggest that ephrin-A1 plays an important role in tumor progression, but the exact function is complex, cell-type dependent and most likely relies on many factors, Ro 25-6981 maleate including its favored receptor EphA2 [44]. Furthermore, the role of ephrin-A1 as a biomarker still remains elusive, and especially in NSCLC further studies are certainly required. Conclusions We have shown that in the present cohort of NSCLC patients S100A4-positive tumors Ro 25-6981 maleate were smaller and more differentiated than tumors without expression. It will be of great interest to examine whether Ro 25-6981 maleate the observed association between S100A4 expression and clinicopathological parameters also influence on patient end result, and this will be investigated when follow-up data are available. Furthermore, we have exhibited that S100A4 induces expression of ephrin-A1 in lung adenocarcinoma cell lines, and that the expression of these Ro 25-6981 maleate potential biomarkers is usually significantly associated in the primary tumor samples. Finally, our findings contribute to an increased understanding of the molecular characteristics of NSCLC, which hopefully will foster improvements in diagnostics, therapeutic decisions and the development of novel therapies. Competing interests The authors declare that they have no competing interests. Authors contributions AKR conceived the study, carried out the cell culture experiments, evaluated immunostained sections, performed data analysis and published the manuscript. ML-I evaluated immunostained sections. GB performed real time RT-PCR analyses and Western blotting. OTB and SKS provided patient material and patient data. GMM conceived the study and participated in writing the manuscript. KB conceived the study, evaluated immunostained sections, participated in data analysis and manuscript drafting. All authors go through and approved the final manuscript. Pre-publication history The pre-publication history for this paper can be utilized here: http://www.biomedcentral.com/1471-2407/12/333/prepub Supplementary Material Additional file 1: Associations between clinicopathological parameters and expression of S100A4, ephrin-A1 and osteopontin. Click here for file(57K, pdf) Additional file 2: Associations between immunohistochemical expression of cytoplasmic and nuclear S100A4 and selected clinicopathological parameters in adenocarcinomas. Click here for file(40K, pdf) Acknowledgements The authors would like to thank Ingjerd Solvoll, Ellen Hellesylt and Tove ?yjord for excellent technical assistance. This work was supported by the Research Council of Norway (grant #191431/V50 to AKR and grant #193375/V50 to GB) and the Norwegian Cancer Society (grant #421852 to GMM)..