Abstract
Simple SummaryLung cancer remains the leading cause of cancer-related deaths worldwide. Herein, the heterogeneous tumor stroma decisively impacts on tumor progression, therapy resistance, and, thus, poor clinical outcome. Among the numerous non-epithelial cells constructing the complex environment of lung carcinomas, mesenchymal stem cells (MSC) gained attraction being stromal precursor cells that could be recruited and ‘educated’ by lung cancer cells to adopt a tumor-associated MSC phenotype, serve as source for activated fibroblasts and presumably for vascular mural cells finally reinforcing tumor progression. Lung-resident MSCs should be considered as ‘local MSCs in stand by’ ready to be arranged within the cancer stroma.Lung-resident mesenchymal stem cells (LR-MSCs) are non-hematopoietic multipotent stromal cells that predominately reside adventitial within lung blood vessels. Based on their self-renewal and differentiation properties, LR-MSCs turned out to be important regulators of normal lung homeostasis. LR-MSCs exert beneficial effects mainly by local secretion of various growth factors and cytokines that in turn foster pulmonary regeneration including suppression of inflammation. At the same time, MSCs derived from various tissues of origins represent the first choice of cells for cell-based therapeutic applications in clinical medicine. Particularly for various acute as well as chronic lung diseases, the therapeutic applications of exogenous MSCs were shown to mediate beneficial effects, hereby improving lung function and survival. In contrast, endogenous MSCs of normal lungs seem not to be sufficient for lung tissue protection or repair following a pathological trigger; LR-MSCs could even contribute to initiation and/or progression of lung diseases, particularly lung cancer because of their inherent tropism to migrate towards primary tumors and metastatic sites. However, the role of endogenous LR-MSCs to be multipotent tumor-associated (stromal) precursors remains to be unraveled. Here, we summarize the recent knowledge how ‘cancer-educated’ LR-MSCs impact on lung cancer with a focus on mesenchymal stem cell fates.
Highlights
Lung cancer is one of the most commonly diagnosed cancers worldwide and with remaining the leading cause of cancer-related deaths, the burden accounts for nearly2 million deaths per year [1,2]
Critically conbetter understanding of how endogenous lung biology, mesenchymal stromal cells (MSCs) contribute to thestrategies local microenvitribute to theAheterogeneity and complexity of lung cancer could foster to manipronment of lung cancer holds the potential to develop strategies to improve lung cancer ulate these cells on site, paving an additional way for the discovery of potential drug targets therapy by targeting Lung-resident mesenchymal stem cells (LR-MSCs) derived stromal cells
LR-MSCs in their native environment turned out to orchestrate the fate of tumor cells
Summary
Lung cancer is one of the most commonly diagnosed cancers worldwide and with remaining the leading cause of cancer-related deaths, the burden accounts for nearly. A detailed smooth muscle cells (SMC) and, impacting on vascular remodeling of newly formed tumor understanding of how LR-MSCs are implicated within the tumor stroma, and, critically contribute to the heterogeneity blood vessels, (ii) acquiring an activated fibroblast Critically conbetter understanding of how endogenous lung biology, MSCs contribute to thestrategies local microenvitribute to theAheterogeneity and complexity of lung cancer could foster to manipronment of lung cancer holds the potential to develop strategies to improve lung cancer ulate these cells on site, paving an additional way for the discovery of potential drug targets therapy by targeting LR-MSCs derived stromal cells. A better understanding of how endogenous lung MSCs contribute to the local microenvironment of lung cancer holds the potential to develop strategies to improve lung cancer
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