Multidimensional analysis to elucidate the possible mechanism of bone metastasis in breast cancer.

BACKGROUND: Breast cancer (BC) patients tend to suffer from distant metastasis, especially bone metastasis. METHODS: All the analysis based on open-accessed data was performed in R software, dependent on multiple algorithms and packages. The RNA levels of specific genes were detected using quantitative Real-time PCR as a method of detecting the RNA levels. To assess the ability of BC cells to proliferate, we utilized the CCK8 test, colony formation, and the 5-Ethynyl-20-deoxyuridine assay. BC cells were evaluated for invasion and migration by using Transwell assays and wound healing assays. RESULTS: In our study, we identified the molecules involved in BC bone metastasis based on the data from multiple BC cohorts. Then, we comprehensively investigated the effect pattern and underlying biological role of these molecules. We found that in the identified molecules, the EMP1, ACKR3, ITGA10, MMP13, COL11A1, and THY1 were significantly correlated with patient prognosis and mainly expressed in CAFs. Therefore, we explored the CAFs in the BC microenvironment. Results showed that CAFs could activate multiple carcinogenic pathways and most of these pathways play an important role in cancer metastasis. Meanwhile, we noticed the interaction between CAFs and malignant, endothelial, and M2 macrophage cells. Moreover, we found that CAFs could induce the remodeling of the BC microenvironment and promote the malignant behavior of BC cells. Then, we identified MMP13 for further analysis. It was found that MMP13 can enhance the malignant phenotype of BC cells. Meanwhile, biological enrichment and immune infiltration analysis were conducted to present the effect pattern of MMP13 in BC. CONCLUSIONS: Our result can improve the understanding of researchers on the underlying mechanisms of BC bone metastasis.

Effects of aquaporins on chemosensitivity to cisplatin in ovarian cancer cells.

INTRODUCTION: As water transporters, aquaporins (AQPs) are closely related to other membrane transporters, and water permeability in cell may contribute to chemosensitivity of tumor. To understand the correlation between AQPs and cisplatin (DDP) sensitivity to ovarian cancer cells, effects of DDP on AQPs expression were detected in vitro, and chemosensitivity of DDP was observed in hypertoncity in vitro. METHODS: SKOV3 cells were incubated with DDP, aquaporins blocker mercuric chloride, or in hypertonicity, and cell proliferation inbihition was measured by MTT. Effects of DDP on AQPs mRNA expression cancer cell SKOV3 were measured by RT-PCR. RESULTS: MTT analyses showed that aquaporin blocker and hypertonicity increased the sensitivity of SKOV3 to DDP. The effects of DDP on AQPs expression were different between aquaporin subtypes: following an increase in the incubation time, the expression of AQP1 mRNA decreased significantly, but expression of AQP3 and AQP8 increased. CONCLUSION: Our studies have showed that different subtypes of AQPs play different roles in ovarian cancer cell in vitro, and which suggested that AQPs might be associated with chemotherapy sensitivity of ovarian cancer.