Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.
Physical activity and the prevention of weight gain decrease breast cancer incidence and improve survival. Unraveling the biological mechanisms underlying these cancer prevention effects is difficult because activity and dietary restriction are often linked. The goal of this study was to determine whether physical activity (PA), preventing weight gain via energy restriction (ER), or the combination was most effective in delaying tumor growth, reducing metastatic progression, and improving survival in the 4T1.2 mammary tumor model. Furthermore, we determined whether any of these interventions prevented the expansion of protumor immunosuppressive cells and altered the tumor microenvironment (TME). Female BALB/c mice (n ¼ 7-20/group) were randomized to sedentary (SED) or PA wheel cages and fed ad libitum (AL) or 90% of control food intake (ER). After 8 weeks on the interventions, mice were inoculated with 5 Â 10 4 4T1.2 luc cells into the 4th mammary fat pad and continued on their respective intervention. PAþER significantly delayed primary tumor growth (final tumor volume, 0.193 AE 0.042 vs. 0.369 AE 0.049 cm 3 , P < 0.001), reduced metastatic burden in the lungs (0.72 AE 0.36 vs. 16.27 AE 6.98, P ¼ 0.054) and increased survival (median survival, 68 vs 40 days, P ¼ 0.043) compared with SEDþAL mice. PAþER also reduced the expression level of metastatic and immunosuppressive genes and resulted in favorable changes in immune cell infiltrates in the tumor. These data suggest that both PA and ER are needed to reduce tumor growth, delay metastatic progression, and improve survival, and that this protection is associated with changes in immune-mediated mechanisms.
BackgroundMakorin RING zinc finger-2 (MKRN2) belongs to the makorin RING zinc finger family and is a novel ubiquitin E3 ligase targeting the p65 subunit of NF-κB to negatively regulate inflammatory responses; however, the relationship between MKRN2 and tumorigenesis remains unclear. In this study, we clarified the role of MKRN2 in non-small cell lung cancer (NSCLC).MethodsTumor specimens collected from 261 NSCLC patients from 2013 to 2017 were retrieved from the Pathology Archive of the First Affiliated Hospital of China Medical University, and we performed assays to evaluate MKRN2 expression and to determine the impact of MKRN2 silencing and overexpression on NSCLC-cell migration and invasion.ResultsWe demonstrated that MKRN2 expression was associated with lymph node metastasis, p-TNM stage, cancer-cell differentiation, and poor prognosis. By altering the expression of MKRN2 in selected cell lines, we found that MKRN2 inhibited cell migration and invasion through downregulation of the PI3K/Akt pathway.ConclusionsThese results suggested that MKRN2 inhibited NSCLC progression by reducing the metastatic potential of cancer cells. Our findings provide critical insight into the association of MKRN2 expression with favorable clinicopathological characteristics in NSCLC patients and suggested that MKRN2 plays a role in inhibiting NSCLC development.
Background/Aims: Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the occurrence and development of various tumors, thereby attracting increasing attention from researchers. The important biological functions of lncRNAs have been recognized gradually, but their mechanism in cervical cancer remains unclear. Methods: Differentially expressed lncRNAs in cervical cancer and para-carcinoma tissues were identified by screening using an lncRNA array, and candidate lncRNAs were verified by quantitative real-time PCR. A series of bioinformatics and molecular biological methods were adopted to investigate the interactions among lncRNAs, microRNAs (miRNAs), and miRNA target genes in cervical cancer. Cell viability was measured using a Cell Counting Kit-8 assay. Results: DLG1-AS1 was the most significantly up-regulated lncRNA in cervical cancer tissues, and it was confirmed that cervical cancer patients with high DLG1-AS1 expression had a poor prognosis. Down-regulation of DLG1-AS1 expression suppressed the proliferation of cervical cancer cells. Further investigation revealed that DLG1-AS1 eliminated the inhibition of miR-107 on the expression of its target gene ZHX1 by competitively binding to miR-107. Moreover, rescue assays proved that the effect of DLG1-AS1 on the proliferation of cervical cancer cells was dependent on miR-107. Conclusion: DLG1-AS1/miR-107/ZHX1 can form a competitive endogenous RNA network that regulates the proliferation of cervical cancer cells, resulting in tumor progression.
Key Points LMO2 is deacetylated by the NAMPT/SIRT2 pathway. LMO2 deacetylation is essential for LIM domain binding 1 binding and TAL1 complex activation during hematopoiesis and T-ALL leukemogenesis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.