Bone invading NSCLC cells produce IL-7: mice model and human histologic data

BMC Cancer

Research Article

Paolo Giannoni¹  Lucia D'Amico²  Ilaria Roato²  Riccardo Ferracini³  Davide Caldo⁴  Emanuela Morello⁵  Paolo Buracco⁵  Rodolfo Quarto⁶  Antonio Mussa⁷  Laura Godio⁸  Luigi Molfetta⁹ 

[1] ABC Advanced Biotechnology Center, Genoa, Italy;CeRMS (Center for Experimental Research and Medical Studies) University of Turin and A.O.U. San Giovanni Battista, Turin, Italy;CeRMS (Center for Experimental Research and Medical Studies) University of Turin and A.O.U. San Giovanni Battista, Turin, Italy;Department of Orthopaedics, A.O.U. San Giovanni Battista, Turin, Italy;CeRMS (Center for Experimental Research and Medical Studies) University of Turin and A.O.U. San Giovanni Battista, Turin, Italy;Department of Orthopaedics, A.O.U. San Giovanni Battista, Turin, Italy;Department of Experimental Medicine (DIMES), University of Genoa, Italy;Department of Animal Pathology, University of Turin, Grugliasco, Italy;Department of Experimental Medicine (DIMES), University of Genoa, Italy;Department of Medical Oncology, A.O.U. San Giovanni Battista, Turin, Italy;Department of Pathology, A.O.U. San Giovanni Battista, Turin, Italy;University of Genoa - Department of Motor Sciences, Italy;

关键词: A549 Cell;    Bone Metastasis;    Human Bone;    NSCLC Cell;    Bone Invasion;   

DOI  :  10.1186/1471-2407-10-12

 received in 2009-07-28, accepted in 2010-01-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundBone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies.MethodsWe used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison.ResultsAt 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant.ConclusionsWe demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

【 授权许可】

Unknown   
© Roato et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.