Pten in stromal fibroblasts suppresses mammary epithelial tumours

BackgroundFibroblast activation protein (FAP) is commonly expressed in activated stromal fibroblasts in various epithelial tumours. Recently, 68Ga-FAPI-04 has been used for tumour imaging in positron emission tomography/computed tomography (PET/CT). This study aimed to compare the diagnostic performances of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT in hepatocellular carcinoma (HCC), and to assess factors associated with 68Ga-FAPI-04 uptake in HCC.Materials and MethodsTwenty-nine patients with suspiciously HCC who received both 18F-FDG and 68Ga-FAPI-04 PET/CT were included in this retrospective study. The results were interpreted by two experienced nuclear medicine physicians independently. The maximum and mean standardized uptake values (SUVmax and SUVmean) were measured in the lesions and liver background, respectively. The tumour-to-background ratio (TBR) was then calculated as lesion’s SUVmax divided by background SUVmean.ResultsA total of 35 intrahepatic lesions in 25 patients with HCC were finally involved in the statistical analysis. 68Ga-FAPI-04 PET/CT showed a higher sensitivity than 18F-FDG PET/CT in detecting intrahepatic HCC lesions (85.7% vs. 57.1%, P = 0.002), including in small (≤ 2 cm in diameter; 68.8% vs. 18.8%, P = 0.008) and well- or moderately-differentiated (83.3% vs. 33.3%, P = 0.031) tumors. SUVmax was comparable between 68Ga-FAPI-04 and 18F-FDG (6.96 ± 5.01 vs. 5.89 ± 3.38, P > 0.05), but the TBR was significantly higher in the 68Ga-FAPI-04 group compared with the 18F-FDG group (11.90 ± 8.35 vs. 3.14 ± 1.59, P < 0.001). SUVmax and the TBR in 68Ga-FAPI-04 positive lesions were associated with tumour size (both P < 0.05), but not the remaining clinical and pathological features (all P > 0.05).Conclusions68Ga-FAPI-04 PET/CT is more sensitive than 18F-FDG PET/CT in detecting HCC lesions, and 68Ga-FAPI-04 uptake is correlated mainly with tumour size.

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Stromal fibroblasts influence human mammary epithelial cell morphogenesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0401376101 ◽

2004 ◽

Vol 101 (14) ◽

pp. 4723-4724 ◽

Cited By ~ 10

Author(s):

D. Medina

Keyword(s):

Epithelial Cell ◽

Mammary Epithelial Cell ◽

Human Mammary Epithelial Cell ◽

Mammary Epithelial ◽

Cell Morphogenesis ◽

Stromal Fibroblasts ◽

Human Mammary Epithelial

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A pleiotropic role for FGF signaling in mammary gland stromal fibroblasts

10.1101/565267 ◽

2019 ◽

Cited By ~ 1

Author(s):

Zuzana Koledova ◽

Jakub Sumbal

Keyword(s):

Extracellular Matrix ◽

Mammary Gland ◽

Mammary Epithelium ◽

Branching Morphogenesis ◽

Mammary Epithelial ◽

Fibroblast Proliferation ◽

Fgf Signaling ◽

Stromal Fibroblasts ◽

Fibroblast Migration ◽

And Migration

AbstractFibroblast growth factor (FGF) signaling is crucial for mammary gland development. While multiple roles for FGF signaling in the epithelium were described, the function of FGF signaling in mammary stroma has not been elucidated. In this study, we investigated FGF signaling in mammary fibroblasts. We found that mammary fibroblasts express FGF receptors 1 and 2 and respond to FGF ligands. In particular, FGF2 and FGF9 induce sustained ERK1/2 signaling and promote fibroblast proliferation and migration in 2D. Intriguingly, only FGF2 induces fibroblast migration in 3D extracellular matrix (ECM) through regulation of actomyosin cytoskeleton and promotes force-mediated collagen remodeling by mammary fibroblasts. Moreover, FGF2 regulates production of ECM proteins by mammary fibroblasts, including collagens, fibronectin, osteopontin, and matrix metalloproteinases. Finally, we show that FGF2 signaling in mammary fibroblasts enhances fibroblast-induced branching of mammary epithelium. Our results demonstrate a pleiotropic role for FGF signaling in mammary fibroblasts with implications for regulation of mammary stromal functions and epithelial branching morphogenesis.Summary statementFGF signaling in mammary fibroblasts regulates fibroblast proliferation, migration, extracellular matrix production and remodeling, and fibroblast-mediated mammary epithelial branching morphogenesis.

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