Adipocytes are the main stromal cells in the tumor microenvironment. In addition to serving as energy stores for triglycerides, adipocytes may function as an active endocrine organ. The crosstalk between adipocytes and cancer cells was shown to promote the migration, invasion and proliferation of cancer cells and to cause phenotypic and functional changes in adipocytes. Tumor-derived soluble factors, such as TNF-α, plasminogen activator inhibitor 1, Wnt3a, IL-6, and exosomal microRNAs (miRNA/miRs), including miR-144, miR-126, miR-155, as well as other miRNAs, have been shown to act on adipocytes at the tumor invasion front, resulting in the formation of cancer-associated adipocytes (CAAs) with diminished reduced terminal differentiation markers and a dedifferentiated phenotype. In addition, the number and size of CAA lipid droplets have been found to be significantly reduced compared with those of mature adipocytes, whereas inflammatory cytokines and proteases are overexpressed. The aim of the present review was to summarize the latest findings on the biological changes of CAAs and the potential role of tumor-adipocyte crosstalk in the formation of CAAs, in the hope of providing novel perspectives for breast cancer treatment.
Cancer-associated adipocytes (CAAs), which are adipocytes transformed by cancer cells, are of great importance in promoting the progression of breast cancer. However, the underlying mechanisms involved in the crosstalk between cancer cells and adipocytes are still unknown. Here we report that CAAs and breast cancer cells communicate with each other by secreting the cytokines leukemia inhibitory factor (LIF) and C-X-C subfamily chemokines (CXCLs), respectively. LIF is a pro-inflammatory cytokine secreted by CAAs, which promotes migration and invasion of breast cancer cells via the Stat3 signaling pathway. The activation of Stat3 induced the secretion of glutamic acid-leucine-arginine (ELR) motif CXCLs (CXCL1, CXCL2, CXCL3 and CXCL8) in tumor cells. Interestingly, CXCLs in turn activated the ERK1/2/NF-κB/Stat3 signaling cascade to promote the expression of LIF in CAAs. In clinical breast cancer pathology samples, the up-regulation of LIF in paracancerous adipose tissue was positively correlated with the activation of Stat3 in breast cancer. Furthermore, we verified that adipocytes enhanced lung metastasis of breast cancer cells, and the combination of EC330 (targeting LIF) and SB225002 (targeting C-X-C motility chemokine receptor 2 (CXCR2)) significantly reduced lung metastasis of breast cancer cells
in vivo
. Our findings reveal that the interaction of adipocytes with breast cancer cells depends on a positive feedback loop between the cytokines LIF and CXCLs, which promotes breast cancer invasion and metastasis.
The prevalence of attention deficit hyperactivity disorder (ADHD) among children and the ineffective traditional treatment methods have become difficult social problems nowadays. From the perspective of art therapy, this paper has put forward the concept of interaction, and considering the clinical experience related to the pathology of children with ADHD, focused on the analysis of the requirements, design and implementation methods of immersive interactive animation in the treatment of ADHD, so as to provide theoretical basis for interdisciplinary research of animation arts in the field of ADHD treatment.
We propose an integrated device based on multi-plane light conversion (MPLC) for cyclic mode permutation (CMP). Both 3-mode and 6-mode CMP schemes are demonstrated with excellent simulated performance.
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