Abstract
Growing importance has been attributed to interactions between tumors, the stromal microenvironment and adult mesenchymal stem cells. Adipose-derived stem cells (ASCs) are routinely employed in regenerative medicine and in autologous fat transfer procedures. To date, clinical trials have failed to demonstrate the potential pro-oncogenic role of ASC enrichment. Nevertheless, some pre-clinical studies from in vitro and in vivo models have suggested that ASCs act as a potential tumor promoter for different cancer cell types, and support tumor progression and invasiveness through the activation of several intracellular signals. Interaction with the tumor microenvironment and extracellular matrix remodeling, the exosomal release of pro-oncogenic factors as well as the induction of epithelial-mesenchymal transitions are the most investigated mechanisms. Moreover, ASCs have also demonstrated an elective tumor homing capacity and this tumor-targeting capacity makes them a suitable carrier for anti-cancer drug delivery. New genetic and applied nanotechnologies may help to design promising anti-cancer cell-based approaches through the release of loaded intracellular nanoparticles. These new anti-cancer therapies can more effectively target tumor cells, reaching higher local concentrations even in pharmacological sanctuaries, and thus minimizing systemic adverse drug effects. The potential interplay between ASCs and tumors and potential ASCs-based therapeutic approaches are discussed.
Highlights
In the last decade, the tumor microenvironment has gained more and more relevance in cancer biology and progression [1]
Different and conflicting data from the literature indicate that Adipose-derived stem cells (ASCs) can favor tumor growth and progression
Seo et al described the inhibitory effect of exosomal miR-503-3p from ASC-conditioned medium on breast cancer cell proliferation, and the self-renewal of cancer stem cells (CSC)
Summary
The tumor microenvironment has gained more and more relevance in cancer biology and progression [1]. TGF-β1 secretion promotes an immunomodulatory effect, and increase extra-cellular matrix deposition and collagen organization [30] All these particular characteristics of ASCs have encouraged their use in many clinical situations, in those tissues where healing is impaired by inadequate blood supply and a chronic inflammatory state, such as in radio-treated tissues [31]. ASCs’ secretion of pro-angiogenetic growth factors and chemokines like PDGF, VEGF c-kit is useful to increase blood supply in poorly vascularized tissues, but at the same time, it could induce the proliferation of endothelial cells and foster the development of a tumor-supporting vascular network, which could lead to the disease spreading [36,37,38]. We review up-to-date clinical studies using ASCs in oncological patients, in order to evaluate whether ASCs could be considered a safe drug-carrier in oncological settings
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