Exosomes derived from bone marrow mesenchymal stem cells promote proliferation and migration via upregulation yes-associated protein/transcriptional coactivator with PDZ binding motif expression in breast cancer cells.

Bone marrow mesenchymal stem cells (BM-MSCs), with the properties of self-renewal and pluripotency, can migrate to the tumor sites and exert complex effects on tumor progression and communications by releasing exosomes. However, to our knowledge, only a few studies have reported the effects of BM-MSCs exosomes on breast cancer cells development. Here, utilizing exosomes isolated from in vitro BM-MSCs, we systematically investigated this issue in a breast cancer cell line. In this study, we found that BM-MSCs exosomes are actively incorporated by breast cancer cell MDA-MB-231 cells and subsequently promote MDA-MB-231 cells proliferation and migration. Mechanistically, we further found Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) which are Hippo signaling components were involved in this promoting progress. Consistently, YAP and TAZ knockdown could significantly reverse breast cancer cells proliferation and migration improved by BM-MSCs exosomes. Taken together, our findings demonstrated a new mechanism through which BM-MSCs-derived exosomes may contribute to breast cancer cells proliferation and migration, which might provide an evidence for novel drug discovery based on exosomes and Hippo signaling.

STC2 suppresses triple-negative breast cancer migration and invasion by inhibition on EMT and promotion on cell apoptosis.

To investigate the effects of higher cellular stanniocalcin 2 (STC2) on suppressing the migration and invasion but promoting the apoptosis of triple-negative breast cancer (TNBC). STC2 in TNBC and the para-carcinoma tissues were analyzed by immunohistochemistry (IHC), while the mRNA level was measured by qPCR. Over-expressing or silencing STC2 was established in MDA-MB-231 cells. Epithelial mesenchymal transition (EMT) related proteins, cell migration, invasion, proliferation and apoptosis were detected. MDA-MB-231 with over-expressing or silencing STC2 were injected into nude mice to formatting tumors, and then EMT related proteins were measured by IHC. Lower STC2 expressed in TNBC tissues than in the para-carcinoma tissues. Silencing STC2 promoted EMT of TNBC cell MDA-MB-231, as well as cell migration, invasion and proliferation, but suppressed MDA-MB-231 apoptosis, while over-expressing STC2 had the opposite results, which might be related to PKC/PI3K/AKT/mTOR pathway. STC2 was the protective gene in TNBC, by suppressing migration and invasion to inhibit MDA-MB-231 cell EMT but promote cell apoptosis, in order to suppress TNBC progression.

In vitro Function Study of Different Negative Charge Pullulan Nanoparticles for Sentinel Lymph Node Angiography.

BACKGROUND: Many dyes or radioactive markers used for sentinel lymph node (SLN) have the shortcomings of false positive and radiation injury. Indocyanine green (ICG) seems to have a lower false positive rate and tissue damage, without a clear field of vision during the operation. METHODS: For the shortcomings, we successfully synthesized three anionic pullulan materials, changed the degree of hydrophobic for size controlling (< 50nm) to prepare CHP nanoparticles (NPs) and changed the succinyl degree to prepare CHPC NPs with different negative surface potential. RESULTS: The size of those NPs were less than 50nm under (transmission electron microscope) TEM, with hydrodynamic size of 90.67 ± 2.2 nm of CHP, 105.8 ± 1.7 nm of CHPC1 and 115.9 ± 2.3 nm of CHPC2. Moreover, the Zeta potential of CHP, CHPC1 and CHPC2 were -1.9 ± 0.2 mV, -9.6 ± 0.3 mV and -19.4 ± 0.7 mV. The size of ICG-loading CHP, CHPC1 and CHPC2 NPs increased to 109.4 ± 2.7 nm, 113.8 ± 1.2 nm and 30.6 ± 3.5 nm, as the zeta potential decreased to -2.7 ± 0.4 mV, -12.5 ± 1.6 mV and -23.1 ± 1.2 mV. With the increasing degree of succinyl, the size increased and the zeta potential decreased. At the same time, the higher degree of succinyl drug-loading NPs have lower release and have increased the stability of ICG. We found that the blank-NPs had no significant toxicity to normal cells (HSF), as the ICG@CHP group had larger toxicity than the CHPCs and control. Moreover, the cellular uptake was decreased with the increased degree of succinyl. CONCLUSION: In this study, we successfully prepared CHPC2 carriers with the maximum negative surface charge, for follow-up research and providing new ideas for SLN.

Circ_0108942 Regulates the Progression of Breast Cancer by Regulating the MiR-1178-3p/TMED3 Axis.

BACKGROUND: Breast cancer (BC) has posed a fatal threat to women's lives and the search for new methods of diagnosis and treatment is an important way to break the bottleneck of high mortality in BC. Circular RNAs (circRNAs) have been confirmed to be aberrantly expressed in several types of cancers, and this study is intended to elucidate the role and mechanism of circ_0108942 in BC. MATERIALS AND METHODS: The levels of circ_0108942, microRNA-1178-3p (miR-1178-3p), and transmembrane p24 trafficking protein 3 (TMED3) were measured using real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. Meanwhile, the cell proliferation, migration, invasion, angiopoiesis, and apoptosis were analyzed using 5-ethynyl-2'-deoxyuridine (EdU), transwell, tubule formation, and flow cytometry assays. Protein levels were determined by western blot. In addition, we used dual-luciferase reporter and RNA pull-down assays to identify the interplay between miR-1178-3p and circ_0108942 or TMED3. Lastly, the impact of circ_0108942 on the growth of BC tumors in vivo was analyzed by xenograft models. RESULTS: Circ_0108942 and TMED3 were notably upregulated in BC, and the miR-1178-3p was downregulated. Functionally, silencing circ_0108942 suppressed cell proliferation, migration, invasion and promoted apoptosis in BC cells. In mechanism, circ_0108942 regulated TMED3 expression by sponging miR-1178-3p. Meanwhile, circ_0108942 knockdown also greatly constrained tumor growth in vivo. CONCLUSION: Circ_0108942 boosted BC progression by regulating miR-1178-3p and thus upregulating TMED3.

Development of a model for predicting mortality of breast cancer admitted to Intensive Care Unit.

Background: There is still not a mortality prediction model built for breast cancer admitted to intensive care unit (ICU). Objectives: We aimed to build a prognostic model with comprehensive data achieved from eICU database. Methods: Outcome was defined as all-cause in-hospital mortality. Least absolute shrinkage and selection operator (LASSO) was conducted to select important variables which were then taken into logistic regression to build the model. Bootstrap method was then conducted for internal validation. Results: 448 patients were included in this study and 79 (17.6%) died in hospital. Only 5 items were included in the model and the area under the curve (AUC) was 0.844 (95% confidence interval [CI]: 0.804-0.884). Calibration curve and Brier score (0.111, 95% CI: 0.090-0.127) showed good calibration of the model. After internal validation, corrected AUC and Brier score were 0.834 and 0.116. Decision curve analysis (DCA) also showed effective clinical use of the model. The model can be easily assessed on website of https://breastcancer123.shinyapps.io/BreastCancerICU/. Conclusions: The model derived in this study can provide an accurate prognosis for breast cancer admitted to ICU easily, which can help better clinical management.