Brain and Breast Cancer Cells with PTEN Loss of Function Reveal Enhanced Durotaxis and RHOB Dependent Amoeboid Migration Utilizing 3D Scaffolds and Aligned Microfiber Tracts

Wieland, Annalena; Strissel, Pamela L.; Schorle, Hannah; Bakırcı, Ezgi; Janzen, Dieter; Beckmann, Matthias W.; Eckstein, Markus; Dalton, Paul D.; Strick, Reiner

doi:10.3390/cancers13205144

Cited by 7 publications

(3 citation statements)

References 103 publications

(134 reference statements)

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“…Additionally, it ranks among the most frequently deleted tumor suppressor genes in human cancer cells (Leslie and Downes 2004 ; Haddadi et al 2018 ). MDA-MB-231 cells express wild-type PTEN (Hlobilkova et al 2006 ; Wieland et al 2021 ). In addition, Razmara et al suggested that MKP-3 negatively modulates the PI3K-dependent AKT phosphorylation (Razmara et al 2012 ).…”

Section: Resultsmentioning

confidence: 99%

Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

Kim,

Kim

2024

Animal Cells and Systems

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Breast cancer is a frequently occurring malignant tumor that is one of the leading causes of cancer-related deaths in women worldwide. Monoclonal antibodies that block programed cell death 1 (PD-1)/programed cell death ligand 1 (PD-L1) – a typical immune checkpoint – are currently the recommended standard therapies for many advanced and metastatic tumors such as triple-negative breast cancer. However, some patients develop drug resistance, leading to unfavorable treatment outcomes. Therefore, other approaches are required for anticancer treatments, such as downregulation of PD-L1 expression and promotion of degradation of PD-L1. Scoparone (SCO) is a bioactive compound isolated from Artemisia capillaris that exhibits antitumor activity. However, the effect of SCO on PD-L1 expression in cancer has not been confirmed yet. This study aimed to evaluate the role of SCO in PD-L1 expression in breast cancer cells in vitro. Our results show that SCO downregulated PD-L1 expression in a dose-dependent manner, via AKT inhibition. Interestingly, SCO treatment did not alter PTEN expression, but increased the expression of mitogen-activated protein kinase phosphatase-3 (MKP-3). In addition, the SCO-induced decrease in PD-L1 expression was reversed by siRNA-mediated MKP-3 knockdown. Collectively, these findings suggest that SCO inhibited the expression of PD-L1 in breast cancer cells by upregulating MKP-3 expression. Therefore, SCO may serve as an innovative combinatorial agent for cancer immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

Kim,

Kim

2024

Animal Cells and Systems

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“…[ 23 ] Moreover, U87 glioma cells resemble a skating snail phenotype due to durotaxis of aligned PCL fibers. [ 24 ] The term skating snail refers to quick changes in morphology from moving around toward long attached cells along the fibers and again scrolling. Even though the box design is more complex than the aligned linear PCL fibers, the morphology and behavior of U87 cells remained the same (Figure 1C; and Video S1, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

Primary Glial Cell and Glioblastoma Morphology in Cocultures Depends on Scaffold Design and Hydrogel Composition

et al. 2023

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Abstract3D cell cultures better replicate the in vivo environment compared to 2D models. Glioblastoma multiforme, a malignant brain tumor, highly profits from its cellular environment. Here, the U87 glioblastoma cell line in the presence/absence of primary astrocytes is studied. Thiolated hyaluronic acid (HA‐SH) hydrogel reinforced with microfiber scaffolds is compared to Matrigel. Hyaluronic acid is a major extracellular matrix (ECM) component in the brain. Poly(ɛ‐caprolactone) (PCL) scaffolds are written by meltelectrowriting in a box and triangular shaped design with pore sizes of 200 µm. Scaffolds are composed of 10‐layers of PCL microfibers. It is found that scaffold design has an impact on cellular morphology in the absence of hydrogel. Moreover, the used hydrogels have profound influences on cellular morphology resulting in spheroid formation in HA‐SH for both the tumor‐derived cell line and astrocytes, while cell viability is high. Although cocultures of U87 and astrocytes exhibit cell–cell interactions, polynucleated spheroid formation is still present for U87 cells in HA‐SH. Locally restricted ECM production or inability to secrete ECM proteins may underlie the observed cell morphologies. Thus, the 3D reinforced PCL‐HA‐SH composite with glioma‐like cells and astrocytes constitutes a reproducible system to further investigate the impact of hydrogel modifications on cellular behavior and development.

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“…Recent studies ( 27 - 29 ) have shown that mTOR is related to tumorigenesis and development and can control the expression of the c-myc gene, thereby controlling the transcription and translation of cellular ribosomal proteins. mTOR is highly expressed in prostate cancer and breast cancer tissues, which may be closely related to tumor formation and active cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

The effects of the tumor suppressor gene PTEN on the proliferation and apoptosis of breast cancer cells via AKT phosphorylation

Zhang¹,

Ye²,

Lin³

et al. 2023

Transl Cancer Res

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Background The proliferation and apoptosis of cancer cells play important roles in breast carcinomas. However, to date, there have been few reports on the correlation between the expression of PTEN and AKT phosphorylation in breast cancer. This present study investigated the effects of the phosphatase and tensin homology deleted from chromosome 10 ( PTEN ) gene on the proliferation and apoptosis of breast cancer cells through protein kinase B (AKT) phosphorylation. Methods Human breast cancer MDA-MB-231 cells were transfected with the pcDNA3.0 control vector or the pcDNA3.0- PTEN vector for 48 hours. The Cell Counting Kit 8 (CCK-8) was used to detect cell survival rates, double staining was performed to detect apoptosis, and Western blot (WB) analysis was conducted to detect protein expression. The effects of PTEN expression on the cell cycle and apoptosis of human breast cancer cell line MDA-MB-231, and on the levels of phosphorylated AKT protein were further analyzed. Moreover, the relationship between the PTEN gene and clinical features were also analyzed. Results The cell survival rate of cells transfected with pcDNA3.0- PTEN was significantly lower than that of cells transfected with the control pcDNA3.0 vector (55.65%±12.18% vs. 97.32%±12.45%, P=0.004). Compared with the pcDNA3.0 group, the apoptosis rate of the pcDNA3.0- PTEN group was significantly increased (20.65±2.18 vs. 2.32±0.45, P=0.001). The expression of PTEN protein in pcDNA3.0- PTEN group was higher than that in the pcDNA3.0 group, and the expression of the AKT and mTOR proteins was significantly lower than that in pcDNA3.0 group (P<0.05). The expression of PTEN in the lymph node metastasis positive group was significantly higher than that in the lymph node metastasis negative group (P<0.05). The expression of the AKT protein in breast cancer was higher than that in normal breast tissue, and the difference was statistically significant (P<0.01). Conclusions Overexpression of the PTEN gene can promote AKT phosphorylation, increase the apoptotic index of breast cancer cells, and reduce the proliferative activity of breast cancer cells. This provided a new direction for the next treatment of breast cancer, but further clinical research is needed.

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Brain and Breast Cancer Cells with PTEN Loss of Function Reveal Enhanced Durotaxis and RHOB Dependent Amoeboid Migration Utilizing 3D Scaffolds and Aligned Microfiber Tracts

Cited by 7 publications

References 103 publications

Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

Primary Glial Cell and Glioblastoma Morphology in Cocultures Depends on Scaffold Design and Hydrogel Composition

The effects of the tumor suppressor gene PTEN on the proliferation and apoptosis of breast cancer cells via AKT phosphorylation

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