Metastasierung und Progressionsmechanismen von Weichteiltumoren

Steinestel, Konrad; Wardelmann, Eva

doi:10.1007/s00292-015-0072-5

Cited by 4 publications

(3 citation statements)

References 20 publications

(28 reference statements)

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“…As a result of a sequentially complex process involving tumor cells, the host, and the tumor microenvironment, tumor recurrence and metastasis have long been important obstacles in cancer therapy and a major focus of cancer research [ 3 ]. The tumor microenvironment is a distinguishing feature of the tumor; it is a local homeostatic environment formed of tumor-infiltrated immune cells, stromal cells, and t active mediators released by these cells, all of which play an important role in tumor progression [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Breast Cancer Exosome-Derived miR-425-5p Induces Cancer-Associated Fibroblast-Like Properties in Human Mammary Fibroblasts by TGFβ1/ROS Signaling Pathway

Zhu

Dou

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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The connection between the cellular microenvironment and tumor cells is crucial for tumor progression. However, the process by which normal fibroblasts (NFs) become cancer-associated fibroblasts (CAFs) is unknown, and mounting evidence suggests that some microRNAs (miRNAs) have an important role in converting NFs into CAFs. Breast cancer (BC) has been proven to have enhanced miR-425-5p expression in order to support progression. We discovered that human mammary fibroblasts (HMFs) could uptake BC cell line-derived exosomes to change their properties, promoting the switch to the CAF phenotype and increasing cell motility, as evidenced by an increase in CAF activation-related marker protein expression and cell proliferation, invasion, and migration. Transfection of exosomes is obtained from BC cells, and miR-425-5p inhibitors suppressed the aforementioned effects as well as lowered chemokine levels and gene expression related with proliferation and metastasis. By suppressing the expression of its target gene TGFβRII (TGFβ1 receptor), miR-425-5p enhanced the transition of HMFs to the CAF phenotype. MDA-MB-231 cells and CAFs stimulated by HMF absorption of MDA-MB-23-derived exosomes showed similar proliferation, invasion, migration, and expression of -SMA, FAP, CXCL1, IL-6, TGFβ1, P21, P27, Ki67, vimentin, E-cadherin, N-cadherin, α-catenin, fibronectin, and MMP-2. TGFβ1 overexpression enhanced ROS production. Finally, we found that HMFs transiently transfected with miR-425-5p can promote tumor growth in vivo. Finally, these findings provide fresh insight on miR-425-5p as an important mediator of the interaction between BC cells and stroma.

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Section: Introductionmentioning

confidence: 99%

Breast Cancer Exosome-Derived miR-425-5p Induces Cancer-Associated Fibroblast-Like Properties in Human Mammary Fibroblasts by TGFβ1/ROS Signaling Pathway

Zhu

Dou

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The incidence of STS is relatively low – with estimated 4–5 cases per 100,000 per year ( Stiller et al, 2013 ) – but the 5-year survival is only around 50% ( Ferrari et al, 2011 ). Although treatment of STS usually consists of a wide resection of the tumor, followed by radio- or chemotherapy in selected cases ( Casali and Blay, 2010 ), relapses and metastases are still an urgent clinical issue ( Steinestel and Wardelmann, 2015 ). Due to the heterogeneity in genetics and phenotypes of the different STS entities, many of the proposed laboratory biomarkers and clinical factors still are insufficient for a satisfying prognostic evaluation of the individual patient’s outcome.…”

Section: Introductionmentioning

confidence: 99%

Elevated HERV-K Expression in Soft Tissue Sarcoma Is Associated with Worsened Relapse-Free Survival

et al. 2018

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A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients. Therefore, in this study the association between expression of HERV-K and HERV-F and the clinicopathological characteristics in a cohort of STSs as well as the patients’ prognosis was evaluated. HERV-K and HERV-F expression was assessed by quantitative real-time PCR in 120 patient specimens. HERV-K and HERV-F expression was significantly correlated (rS = 0.5; p = 6.4 × 10-9; Spearman’s rank bivariate correlation). Also, tumor diameter exhibited a significant negative association to HERV-K and HERV-F expression. Levels of several hypoxia-related RNAs like HIF-1α and miR-210 showed a significant positive correlation with both HERV-K and HERV-F expression. Although in survival analyses no impact of HERV expression on disease-specific survival could be detected, patients with elevated HERV-K expression had a significantly shorter relapse-free survival (p = 0.014, log-rank analysis). In conclusion, we provide evidence for the first time that the increased expression of HERV-K in tumors is associated with STS patients’ prognosis.

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“…The incidence is low, with around 6:100,000 persons between 1973 and 2006 [ 4 ]; however, the survival rate is still low with around 50% after 5 years and 30% after 15 years [ 4 ]. In particular, metastasization is still an urging clinical issue [ 5 ]. Soft tissue sarcomas metastasize preferentially into the lung and the brain, with around 20% of patients having developed metastases at diagnosis [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma Patients

Greither

Wedler

Rot

et al. 2017

IJMS

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The capillary morphogenesis gene 2 (CMG2), also known as the anthrax toxin receptor 2 (ANTXR2), is a transmembrane protein putatively involved in extracellular matrix (ECM) adhesion and tissue remodeling. CMG2 promotes endothelial cell proliferation and exhibits angiogenic properties. Its downregulation is associated with a worsened survival of breast carcinoma patients. Aim of this study was to analyze the CMG2 mRNA and protein expression in soft tissue sarcoma and their association with patient outcome. CMG2 mRNA was measured in 121 tumor samples of soft tissue sarcoma patients using quantitative real-time PCR. CMG2 protein was evaluated in 52 tumor samples by ELISA. CMG2 mRNA was significantly correlated with the corresponding CMG2 protein expression (rs = 0.31; p = 0.027). CMG2 mRNA expression was associated with the mRNA expressions of several ECM and tissue remodeling enzymes, among them CD26 and components of the uPA system. Low CMG2 mRNA expression was correlated with a worsened patients’ disease-specific survival in Kaplan-Meier analyses (mean patient survival was 25 vs. 96 months; p = 0.013), especially in high-stage tumors. A decreased CMG2 expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2 may be an interesting candidate gene for the further exploration of soft tissue sarcoma genesis and progression.

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Metastasierung und Progressionsmechanismen von Weichteiltumoren

Cited by 4 publications

References 20 publications

Breast Cancer Exosome-Derived miR-425-5p Induces Cancer-Associated Fibroblast-Like Properties in Human Mammary Fibroblasts by TGFβ1/ROS Signaling Pathway

Breast Cancer Exosome-Derived miR-425-5p Induces Cancer-Associated Fibroblast-Like Properties in Human Mammary Fibroblasts by TGFβ1/ROS Signaling Pathway

Elevated HERV-K Expression in Soft Tissue Sarcoma Is Associated with Worsened Relapse-Free Survival

CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma Patients

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