Skeletal Muscle Phenotypically Converts and Selectively Inhibits Metastatic Cells in Mice

Parlakian, Ara; Gomaa, Iman; Solly, Sounkary; Ludovic, Arandel; Mahale, Alka; Born, Gustav; Marazzi, Giovanna; Sassoon, David

doi:10.1371/journal.pone.0009299

Cited by 28 publications

(15 citation statements)

References 96 publications

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“…As we found striking differences between cancer cell extravasation within BMi and muscle-mimicking microenvironments, we asked which factors secreted by muscle might be responsible. It is reported that the skeletal muscle microenvironment reduces cancer cell tumorigenicity and elicits paracrine-mediated cytotoxic and cytostatic responses from metastatic cancer cells (30). In particular, several studies identified the A 3 adenosine receptor (A 3 AR), which is expressed by multiple cancer cell types (31), as key in the antimetastatic and protective effect of skeletal muscle cells (32).…”

Section: Generation Of Functional 3d Microvascular Network Within a Bmimentioning

confidence: 99%

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

Jeon

Bersini

Gilardi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

647

549

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A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into themyoblast-containingmatrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine

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Section: Generation Of Functional 3d Microvascular Network Within a Bmimentioning

confidence: 99%

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

Jeon

Bersini

Gilardi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

647

549

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“…4A, B). As pericytes differentiated into myofibers [11,13], we exposed them to myogenic differentiation conditions and examined the expression of myogenin, a marker of cell differentiation [35], and MHC, a myotube marker [36]. We found that only type-2 pericytes differentiated into the muscle lineage (Fig.…”

Section: Type-2 But Not Type-1 Pericytes Differentiate Into Muscle Cementioning

confidence: 91%

Role of Pericytes in Skeletal Muscle Regeneration and Fat Accumulation

Birbrair

Zhang²,

Wang³

et al. 2013

Stem Cells and Development

258

225

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Stem cells ensure tissue regeneration, while overgrowth of adipogenic cells may compromise organ recovery and impair function. In myopathies and muscle atrophy associated with aging, fat accumulation increases dysfunction, and after chronic injury, the process of fatty degeneration, in which muscle is replaced by white adipocytes, further compromises tissue function and environment. Some studies suggest that pericytes may contribute to muscle regeneration as well as fat formation. This work reports the presence of two pericyte subpopulations in the skeletal muscle and characterizes their specific roles. Skeletal muscle from Nestin-GFP/ NG2-DsRed mice show two types of pericytes, Nestin-GFP-/NG2-DsRed + (type-1) and Nestin-GFP + /NG2-DsRed + (type-2), in close proximity to endothelial cells. We also found that both Nestin-GFP-/NG2-DsRed + and Nestin-GFP + /NG2-DsRed + cells colocalize with staining of two pericyte markers, PDGFRb and CD146, but only type-1 pericyte express the adipogenic progenitor marker PDGFRa. Type-2 pericytes participate in muscle regeneration, while type-1 contribute to fat accumulation. Transplantation studies indicate that type-1 pericytes do not form muscle in vivo, but contribute to fat deposition in the skeletal muscle, while type-2 pericytes contribute only to the new muscle formation after injury, but not to the fat accumulation. Our results suggest that type-1 and type-2 pericytes contribute to successful muscle regeneration which results from a balance of myogenic and nonmyogenic cells activation.

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“…Metastatic tumor cells, after extravasation, at a metastatic site, find themselves in foreign microenvironments. Tumor cells are known to be very sensitive to changes in microenvironmental conditions, which can lead to alterations of fundamental properties of these cells [64,65]. Experimental evidence in melanoma suggests that induction of apoptosis by Fas/Fas-ligand at metastatic sites is an important negative regulator of metastasis [66].…”

Section: Dormancy In Metastatic Melanomamentioning

confidence: 99%

Decoding Melanoma Metastasis

Damsky

Rosenbaum

Bosenberg

2010

Cancers

176

138

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Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

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Skeletal Muscle Phenotypically Converts and Selectively Inhibits Metastatic Cells in Mice

Cited by 28 publications

References 96 publications

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

Role of Pericytes in Skeletal Muscle Regeneration and Fat Accumulation

Decoding Melanoma Metastasis

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