Distinct Effects of Adipose-Derived Stem Cells and Adipocytes on Normal and Cancer Cell Hierarchy

Anjanappa, Manjushree; Burnett, Riesa; Zieger, Michael; Merfeld-Clauss, Stephanie; Wooden, William A.; March, Keith L.; Tholpady, Sunil S.; Nakshatri, Harikrishna

doi:10.1158/1541-7786.mcr-16-0055

Cited by 9 publications

(11 citation statements)

References 47 publications

(54 reference statements)

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“…Populations of cancer stem-like cells have been identified in tumors; these cells have acquired the ability for both local invasion as well as metastasis [61] , [62] , [63] . Adipose stem cells have been shown to promote the expansion of cancer stem-like cells in cancer cell lines [64] . To examine the effect of HFD ASCs on cancer stem-like cells within the mixed tumors, we plated isolated single tumor cells from the mixed HFD or CD Met-1 and EO771 tumors in limiting dilution on nonadherent plates to form tumorspheres.…”

Section: Resultsmentioning

confidence: 99%

Obesity-Activated Adipose-Derived Stromal Cells Promote Breast Cancer Growth and Invasion

et al. 2018

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Obese women diagnosed with breast cancer have an increased risk for metastasis, and the underlying mechanisms are not well established. Within the mammary gland, adipose-derived stromal cells (ASCs) are heterogeneous cells with the capacity to differentiate into multiple mesenchymal lineages. To study the effects of obesity on ASCs, mice were fed a control diet (CD) or high-fat diet (HFD) to induce obesity, and ASCs were isolated from the mammary glands of lean and obese mice. We observed that obesity increased ASCs proliferation, decreased differentiation potential, and upregulated expression of α-smooth muscle actin, a marker of activated fibroblasts, compared to ASCs from lean mice. To determine how ASCs from obese mice impacted tumor growth, we mixed ASCs isolated from CD- or HFD-fed mice with mammary tumor cells and injected them into the mammary glands of lean mice. Tumor cells mixed with ASCs from obese mice grew significantly larger tumors and had increased invasion into surrounding adipose tissue than tumor cells mixed with control ASCs. ASCs from obese mice demonstrated enhanced tumor cell invasion in culture, a phenotype associated with increased expression of insulin-like growth factor-1 (IGF-1) and abrogated by IGF-1 neutralizing antibodies. Weight loss induced in obese mice significantly decreased expression of IGF-1 from ASCs and reduced the ability of the ASCs to induce an invasive phenotype. Together, these results suggest that obesity enhances local invasion of breast cancer cells through increased expression of IGF-1 by mammary ASCs, and weight loss may reverse this tumor-promoting phenotype.

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Section: Resultsmentioning

confidence: 99%

Obesity-Activated Adipose-Derived Stromal Cells Promote Breast Cancer Growth and Invasion

et al. 2018

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“…Their pro-angiogenic capacity though the secretion of growth factors (GFs) and chemokines such as vascular endothelial growth factors (VEGF), platelet-derived growth factors (PDGF) c-kit induce proliferation of endothelial cells and development of a tumor-supporting vascular network [6,7,34]. Moreover, ASCs have immune-modulating proprieties mediated by transforming growth factor-β1 (TGF-β1), hepatocyte growth factors (HGF) and interferon-γ (INF-γ) impairing immune-mediated response to tumor [7,12,35,36,37,38,39]. They are also able to induce drug resistance and cell proliferation in the BCCs line MCF-7/ADR (a multidrug-resistant BCCs model) mediated through C-terminal Src kinase (Csk)-binding protein (Cbp) expression [8].…”

Section: Implications Of Ascs and Their Adipokines And Chemokines mentioning

confidence: 99%

Concise Review: Adipose-Derived Stem Cells (ASCs) and Adipocyte-Secreted Exosomal microRNA (A-SE-miR) Modulate Cancer Growth and proMote Wound Repair

Gentile

Garcovich

2019

JCM

121

112

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Adipose-derived stem cells (ASCs) have been routinely used from several years in regenerative surgery without any definitive statement about their potential pro-oncogenic or anti-oncogenic role. ASCs has proven to favor tumor progression in several experimental cancer models, playing a central role in regulating tumor invasiveness and metastatic potential through several mechanisms, such as the paracrine release of exosomes containing pro-oncogenic molecules and the induction of epithelial-mesenchymal transition. However, the high secretory activity and the preferential tumor-targeting make also ASCs a potentially suitable vehicle for delivery of new anti-cancer molecules in tumor microenvironment. Nanotechnologies, viral vectors, drug-loaded exosomes, and micro-RNAs (MiR) represent additional new tools that can be applied for cell-mediated drug delivery in a tumor microenvironment. Recent studies revealed that the MiR play important roles in paracrine actions on adipose-resident macrophages, and their dysregulation has been implicated in the pathogenesis of obesity, diabetes, and diabetic complications as wounds. Numerous MiR are present in adipose tissues, actively participating in the regulation of adipogenesis, adipokine secretion, inflammation, and inter-cellular communications in the local tissues. These results provide important insights into Adipocyte-secreted exosomal microRNA (A-SE-MiR) function and they suggest evaluating the potential role of A-SE-MiR in tumor progression, the mechanisms underlying ASCs-cancer cell interplay and clinical safety of ASCs-based therapies.

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“…TGF- β is also among the main causes of the immunomodulatory effect of ASCs. Immune-mediated response to tumors is impaired by TGF-β1, HGF, IDO, and IFN-γ, which are secreted by ASCs [38,48,49,50,51,52].…”

Section: Introductionmentioning

confidence: 99%

Adipose-Derived Stem Cells in Cancer Progression: New Perspectives and Opportunities

Scioli

Storti

D’Amico

et al. 2019

IJMS

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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.

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Distinct Effects of Adipose-Derived Stem Cells and Adipocytes on Normal and Cancer Cell Hierarchy

Cited by 9 publications

References 47 publications

Obesity-Activated Adipose-Derived Stromal Cells Promote Breast Cancer Growth and Invasion

Obesity-Activated Adipose-Derived Stromal Cells Promote Breast Cancer Growth and Invasion

Concise Review: Adipose-Derived Stem Cells (ASCs) and Adipocyte-Secreted Exosomal microRNA (A-SE-miR) Modulate Cancer Growth and proMote Wound Repair

Adipose-Derived Stem Cells in Cancer Progression: New Perspectives and Opportunities

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