Authors: Huan Bian Shuai Zhang Huanhuan Wu Yixiang Wang
Publish Date: 2015/03/10
Volume: 36, Issue: 6, Pages: 4467-4477
Abstract
The influence of tumor surrounding microenvironment is often neglected when immunohistochemistry is performed to investigate tumor properties and search biomarkers of cancer This study was designed to evaluate whether the influence of tumor microenvironment on biological features of tumor cells should be taken into account for interpretation of the immunohistochemistry data of tumor specimens In this study we showed an example by using three tumor cell lines HeLa WSUHN6 and Tca83 to establish tumorcaused bone destruction models in nude mice and then to investigate the influence of bone marrow microenvironment BMM on biological features of tumor cells Immunohistochemistry results showed that compared with tumor cells located outside of BMM tumor cells located inside of BMM presented huge differences in the expression of inflammationrelated proteins including tumor necrosis factorα TNFα TNF receptorassociated factor protein6 TRAF6 phosphorylatedNFκB p65 pp65 interleukin IL6 and IL11 matrix metalloproteinases including MMP1 MMP2 MMP9 and MMP13 and osteogenesisrelated proteins including runtrelated transcription factor 2 RUNX2 bone sialoprotein BSP and osteocalcin OCN in all the models However when we compared the cell line pair derived from different sites outside and inside of BMM respectively of the same HeLa tumor sample by realtime PCR Western blot and immunocytochemistry the differences aforementioned in tumor tissues were not found In addition we verified that normal human bone marrow could not cause the above changes detected in vivo Our results suggested that tumormodified microenvironment could give the new biological features of the invaded tumor cells Therefore we should consider the influence of the surrounding microenvironment on tumor cells when we analyze tumor properties using immunohistochemistryThe work was supported by the research grants from Special Fund for Development of Capital Health care 2011402502 Nature Science Foundation of Heilongjiang Province China Grant No QC2014C107 and the Ministry of Science and Technology of China under contract International Science Technology Cooperation Program Foundation Grant No 1019
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