Abstract
BackgroundFibroblasts are mesenchymal stromal cells which occur in all tissue types. While their main function is related to ECM production and physical support, they are also important players in wound healing, and have further been recognized to be able to modulate inflammatory processes and support tumor growth. Fibroblasts can display distinct phenotypes, depending on their tissue origin, as well as on their functional state.ResultsIn order to contribute to the proteomic characterization of fibroblasts, we have isolated primary human fibroblasts from human skin, lung and bone marrow and generated proteome profiles of these cells by LC-MS/MS. Comparative proteome profiling revealed characteristic differences therein, which seemed to be related to the cell’s tissue origin. Furthermore, the cells were treated in vitro with the pro-inflammatory cytokine IL-1beta. While all fibroblasts induced the secretion of Interleukins IL-6 and IL-8 and the chemokine GRO-alpha, other inflammation-related proteins were up-regulated in an apparently tissue-dependent manner. Investigating fibroblasts from tumorous tissues of skin, lung and bone marrow with respect to such inflammation-related proteins revealed hardly any conformity but rather individual and tumor type-related variations. However, apparent up-regulation of IGF-II, PAI-1 and PLOD2 was observed in melanoma-, lung adenocarcinoma- and multiple myeloma-associated fibroblasts, as well as in hepatocellular carcinoma-associated fibroblasts.ConclusionsInflammation-related proteome alterations of primary human fibroblasts were determined by the analysis of IL-1beta treated cells. Tumor-associated fibroblasts from different tissue types hardly showed signs of acute inflammation but displayed characteristic functional aberrations potentially related to chronic inflammation. The present data suggest that the state of the tumor microenvironment is relevant for tumor progression and targeted treatment of tumor-associated fibroblasts may support anti-cancer strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/1559-0275-11-41) contains supplementary material, which is available to authorized users.
Highlights
Fibroblasts are mesenchymal stromal cells which occur in all tissue types
Fibroblasts have long been considered as rather simple structural cells contributing to the extracellular matrix (ECM) in connective tissues and responsible for tissue repair during wound healing
Fibroblasts isolated from different tissues, namely from skin, lung and Bone marrow (BM), analyzed by LC-MS/MS based proteome profiling, were compared
Summary
Fibroblasts are mesenchymal stromal cells which occur in all tissue types. While their main function is related to ECM production and physical support, they are important players in wound healing, and have further been recognized to be able to modulate inflammatory processes and support tumor growth. Chronic inflammation may occur when these clearance mechanisms fail This may happen when fibroblasts either inhibit apoptotic processes by producing survival cytokines, or retain the immune cells by the release of specific chemokines [2]. These interactions are mediated through soluble signaling factors such as growth factors, cytokines, chemokines and lipid products, or by direct communication of the cells through integrins [9] ECM-degrading enzymes such as matrix metalloproteinases (MMPs), produced by fibroblasts, contribute to the degradation and remodeling of the tumor environment, thereby supporting tumor progression, including angiogenesis, invasiveness and metastasis [10]
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