Dermatan Sulfate Affects Breast Cancer Cell Function via the Induction of Necroptosis

Abstract

Dermatan sulfate (DS) is widespread in the extracellular matrix (ECM) of animal tissues. This glycosaminoglycan is characterized by a variable structure, which is reflected in the heterogeneity of its sulfation pattern. The sulfate groups are responsible for the binding properties of DS, which determine an interaction profile of this glycan. However, the detailed role of DS in biological processes such as the neoplasm is still poorly understood. The aim of the study was to assess the effects of the structural variants of DS on breast cancer cells. We found that DS isoforms from normal and fibrotic fascia as well as from intestinal mucosa were able to quickly induce oxidative stress in the cytoplasm and affect the mitochondrial function in luminal breast cancer cells. Moreover, the variants caused the necroptosis of the cells most likely via the first of these mechanisms. This death was responsible for a reduction in the viability and number of breast cancer cells. However, the dynamics and intensity of all of the DS variants-triggered effects were strongly dependent on the cell type and the structure of these molecules. The most pronounced activity was demonstrated by those variants that shared structural features with the DS from the tumor niche.

Bibliometric analysis of publications on necroptosis from 2001 to 2021

“…Some studies have established good prognostic models by analyzing necroptosis-associated genes or miRNAs in breast cancer ( Zheng et al, 2022 ). Many papers have been published on the relationship between necroptosis and cancer (including breast, liver, and prostate cancers) in the last 2 years ( Beretta and Zaffaroni, 2022 ; Li et al, 2022 ; Wisowski et al, 2022 ). We conducted a PubMed search for ‘necroptosis and cancer’ and found that the number of articles in 2021 was the highest and continued to increase.…”

Advances in Nanoparticles in the Prevention and Treatment of Myocardial Infarction

“…In the absence of cysteinase 8, receptor-interacting serine/threonine protein kinases (RIPK)-1 and -3 and mixed lineage kinase domain-like protein (MLKL) will form necrosomes, and the cell death signal will switch from apoptosis to necrosis [ 20 ]. RIPK3 phosphorylates MLKL in the necrosomes, prompting its oligomerization reaction and localization to the cell membrane, leading to burst cell membrane and inducing inflammatory response [ 21 ]. As a new pro-inflammatory programmed cell death mode, pyroptosis is characterized by caspase-1 dependence and the release of a large number of pro-inflammatory factors.…”

Differential Expression of Necroptosis-Related Genes with regulating lncRNA in Triple Negative Breast Cancer to Predict Prognosis and Immunotherapy Response

“…On one hand, it is capable of inhibiting proliferation, aggression, and metastasis of malignancy; on the other hand, it stimulates production of reactive oxygen species (ROS) and maintains tumor microenvironment (TME) [23][24][25]. Bench studies have found that the function and survival of luminal or non-luminal BC cells could be impacted by some specific chemical elements which were capable of regulating necroptosis [26][27][28]. Hence, regulation of necroptosis could be a brand-new approach for anti-TNBC therapy.…”