β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

Yin, Hsin‐Ling; Wu, Chun‐Chieh; Lin, Chih-Hung; Chai, Chee‐Yin; Hou, Ming‐Feng; Chang, Shu-Jyuan; Tsai, Hung-Pei; Hung, Wen‐Chun; Pan, Mei-Ren; Luo, Chi-Wen

doi:10.3390/ijms17091432

Cited by 49 publications

(37 citation statements)

References 49 publications

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“…The recruitment period of patients ranged from 1974 to 2014. Among the 22 studies, 7 focused on lung cancer, 24 – 26 , 39 – 42 3 focused on colorectal cancer, 34 , 35 , 43 6 focused on breast cancer, 28 , 29 , 44 – 47 3 involved melanoma, 48 – 50 and 3 involved pancreatic cancer. 33 , 51 , 52 Moreover, 7 studies were performed in China and 3 studies were performed in the USA.…”

Section: Resultsmentioning

confidence: 99%

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis

Sun¹,

Zhou²,

Ma³

et al. 2018

OTT

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Integrin-beta 1 (ITGB1) is aberrantly overexpressed or downregulated in solid cancers; however, its prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore whether ITGB1 expression is correlated with overall survival (OS) and the clinicopathological characteristics of patients with solid cancers. We systematically searched the PubMed, Embase, and Web of Science databases for eligible studies published up to June 1, 2017. In total, 22 studies involving 3,666 patients were included. A sensitivity analysis was performed to assess the validity and reliability of the pooled OS. Among the 22 studies, 7 focused on lung cancer, 3 focused on colorectal cancer, 6 focused on breast cancer, 3 involved melanoma, and 3 involved pancreatic cancer. The pooled results showed that high ITGB1 expression was significantly associated with worse OS in lung cancer (pooled hazard ratio [HR]=1.78, 95% CI: 1.19–2.65, p<0.05) and breast cancer (pooled HR=1.88, 95% CI: 1.46–2.42, p<0.01). In addition, a significant association was observed between high ITGB1 expression and disease-free survival in breast cancer (pooled HR=1.63, 95% CI: 1.17–2.25, p<0.001) and pancreatic cancer (pooled HR=2.49, 95% CI: 1.35–4.61, p<0.001). However, high ITGB1 expression was not related to OS in colorectal cancer, pancreatic cancer, or melanoma. The pooled HRs used to evaluate the prognostic value of increased ITGB1 expression in lung cancer, breast cancer, and pancreatic cancer were not significantly altered, which indicates that the pooled results were robust. The results of this study indicate that the prognostic value of decreased ITGB1 expression varies among solid cancers.

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Section: Resultsmentioning

confidence: 99%

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis

Sun¹,

Zhou²,

Ma³

et al. 2018

OTT

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“…They mediate the cell adhesion to ECM components supporting adhesion of cells grown on two-dimensional surfaces and within three-dimensional matrices [64]. Although integrins consist of α- and β-subunit, incorporated β 1 -integrin seems to play a special role increasing cell migration and invasion, and decreasing sensitivity to anti-cancer drug in triple-negative breast cancer [65]. Overexpression of β 1 -integrin has been demonstrated to improve the activities and functions of several benign cell types [66].…”

Section: Discussionmentioning

confidence: 99%

Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

Warnke

Pietsch

Kopp

et al. 2017

Cell Physiol Biochem

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Background/Aims: Spaceflight impacts on the function of the thyroid gland in vivo. In vitro normal and malignant thyrocytes assemble in part to multicellular spheroids (MCS) after exposure to the random positioning machine (RPM), while a number of cells remain adherent (AD). We aim to elucidate possible differences between AD and MCS cells compared to 1g-controls of normal human thyroid cells. Methods: Cells of the human follicular epithelial thyroid cell line Nthy-ori 3-1 were incubated for up to 72 h on the RPM. Afterwards, they were investigated by phase-contrast microscopy, quantitative real-time PCR and by determination of cytokines released in their supernatants. Results: A significant up-regulation of IL6, IL8 and CCL2 gene expression was found after a 4h RPM-exposure, when the whole population was still growing adherently. MCS and AD cells were detected after 24 h on the RPM. At this time, a significantly reduced gene expression in MCS compared to 1g-controls was visible for IL6, IL8, FN1, ITGB1, LAMA1, CCL2, and TLN1. After a 72 h RPM-exposure, IL-6, IL-8, and TIMP-1 secretion rates were increased significantly. Conclusion: Normal thyrocytes form MCS within 24 h. Cytokines seem to be involved in the initiation of MCS formation via focal adhesion proteins.

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“…Moreover, the linear ultrastructure is dependent on CCL5, which the co-culture of ASC/MDA-MB-231 generates. Specifically, this study aims to connect the existing TNBC research on CCL5 [8], linearized matrix [3], collagen VI [20], and invasive cellular behavior [31].…”

Section: Discussionmentioning

confidence: 99%

“…Integrin β1 is a known driver of TNBC metastasis, and a clinical prognostic of TNBC development [30], by promoting invasion, proliferation, and cell survival. It so follows that silencing integrin β1 in vitro limits the oncogenic ability of MDA-MB-231 cells [31]. The next step in this study was to understand the origin of CCL5, and the main producer of linear matrix.…”

Section: Blocking Ccl5 In Juxtacrine Co-culture Reduces Collagen VI Amentioning

confidence: 99%

Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5

Brett

Sauter

Timmins

et al. 2020

JCM

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The triple-negative breast tumor boundary is made of aligned, linear collagen. The pro-oncogenic impact of linear collagen is well established; however, its mechanism of formation is unknown. An in vitro analogue of the tumor border is created by a co-culture of MDA-MB-231 cells, adipose derived stem cells, and dermal fibroblasts. Decellularization of this co-culture after seven days reveals an extracellular matrix that is linear in fashion, high in pro-oncogenic collagen type VI, and able to promote invasion of reseeded cells. Further investigation revealed linear collagen VI is produced by fibroblasts in response to a paracrine co-culture of adipose derived stem cells and MDA-MB-231, which together secrete high levels of the chemokine CCL5. The addition of monoclonal antibody against CCL5 to the co-culture results in an unorganized matrix with dramatically decreased collagen VI. Importantly, reseeded cells do not exhibit pro-oncogenic behavior. These data illustrate a cellular mechanism, which creates linear extracellular matrix (ECM) in vitro, and highlight a potential role of CCL5 for building striated tumor collagen in vivo.

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β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

Cited by 49 publications

References 49 publications

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis

Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5

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