The connection between the cellular microenvironment and tumor cells is crucial for tumor progression. However, the process by which normal fibroblasts (NFs) become cancer-associated fibroblasts (CAFs) is unknown, and mounting evidence suggests that some microRNAs (miRNAs) have an important role in converting NFs into CAFs. Breast cancer (BC) has been proven to have enhanced miR-425-5p expression in order to support progression. We discovered that human mammary fibroblasts (HMFs) could uptake BC cell line-derived exosomes to change their properties, promoting the switch to the CAF phenotype and increasing cell motility, as evidenced by an increase in CAF activation-related marker protein expression and cell proliferation, invasion, and migration. Transfection of exosomes is obtained from BC cells, and miR-425-5p inhibitors suppressed the aforementioned effects as well as lowered chemokine levels and gene expression related with proliferation and metastasis. By suppressing the expression of its target gene TGFβRII (TGFβ1 receptor), miR-425-5p enhanced the transition of HMFs to the CAF phenotype. MDA-MB-231 cells and CAFs stimulated by HMF absorption of MDA-MB-23-derived exosomes showed similar proliferation, invasion, migration, and expression of -SMA, FAP, CXCL1, IL-6, TGFβ1, P21, P27, Ki67, vimentin, E-cadherin, N-cadherin, α-catenin, fibronectin, and MMP-2. TGFβ1 overexpression enhanced ROS production. Finally, we found that HMFs transiently transfected with miR-425-5p can promote tumor growth in vivo. Finally, these findings provide fresh insight on miR-425-5p as an important mediator of the interaction between BC cells and stroma.
Background To sort out the basic data and imaging examination results of the patients who underwent the Mammotome minimally invasive surgery, and explore the high-risk underlying factors related to cancerization, in order to optimize the minimally invasive surgery population, and reduce the malignant rate. Methods A total of 1188 female patients who came to our hospital from November 2016 to August 2021 for the Mammotome minimally invasive surgery were analyzed retrospectively. According to the inclusion criteria, the clinical data of 1158 patients and 2164 lesions were finally obtained. We summarized the benign and malignant lesions of BI-RADS category 3, BI-RADS category 4a and BI-RADS category 4b by conventional ultrasound, and got 1562, 578 and 24 lesions respectively. By analyzing the clinical basic data, imaging features and pathological diagnosis of patients, the differences between benign and malignant lesions of these three types were evaluated. Results The malignant rates of BI-RADS category 3, BI-RADS category 4a and BI-RADS category 4b patients who underwent the Mammotome minimally invasive surgery were 0.6%(9/1562), 6.4%(37/578) and 8.3%(2/24) respectively. According to statistics, the age of patients with BI-RADS category 3 is generally younger than that of patients with category 4a and category 4b. Comparing all the three types of lesions in pairs, we found that there were statistical differences in the presence or absence of blood flow signals and the status of calcified lesions, among which category 4b blood flow signal accounted for the highest proportion. Among the category 3 of lesions, we also found that the age of menarche in patients with malignant lesions is younger compared with benign lesions. In category 4a lesions, the patients with malignant lesions were older and mainly concentrated between 40 and 50 years old, and the maximum diameter of the lesions was larger. Whether it is category 3 or category 4a malignant lesions, mammography shows that the incidence of category 4a and multifocal calcification is higher. Conclusion Combined with the clinical data and imaging examination results, BI-RADS category 3 patients have excellent results in choosing Mammotome minimally invasive surgery. Patients with BI-RADS category 4a should be alert to the following factors, including age between 40 and 50, older menarche age, lesion site in the outer upper quadrant, mammography grade of 4a or above, and presence of calcification. Minimally invasive surgery is not recommended for patients diagnosed as BI-RADS category 4b.
Purpose Age has been confirmed to be a very aggressive biological factor and associated with poor prognosis of breast cancer (BC) patients, but the effect of pathological complete response (pCR) rate after neoadjuvant chemotherapy (NAC) is still controversial, with the development of time, young women breast cancer(YWBC) gradually into people's vision, the understanding of YWBC(≤35y) is scarce. This study compares and evaluates the clinical characteristics and pCR rate after NAC in YWBC and other age women with breast cancer. Patients and methods We retrospectively analyzed the clinicopathological data, molecular subtypes, chemotherapy regimen, and pCR rates of 1424 non-metastatic BC patients from the Affiliated Cancer Hospital of Harbin Medical University from January 1, 2012, to December 31, 2019. Categorical data were compared using the chi-square test and Fisher's exact test for multivariate data using Logistic regression models. Any predictor variable with P <0.05 in the univariate analysis was included in the multivariate regression analysis to study the relationship between different age groups and pCR. Results A total of 879 patients in this study were eligible for analysis, and 71(8.1%) female patients were ≤35 years old.YWBC were more likely to get pCR (25.4%vs15.6%, P= 0.033). The proportion of patients with a higher clinical stages was higher. Compared with elderly patients, YWBC patients were more likely to undergo breast-conserving surgery(BCS), multivariate analyses found similar results in different age groups, and more patients with Her-2 positive and triple-negative breast cancer (TNBC). In the whole group, Age, PR expression, HER-2 expression, KI67 expression, and clinical stage were the independent predictors of pCR after NAC in BC patients (P <0.05). Conclusion Our study found that age is the main factor affecting the achievement of pCR in patients with BC. YWBC has a higher clinical stage and a high proportion of HER-2 positive patients, which is the leading cause of poor prognosis.YWBC has a higher effect on chemotherapy therapy. We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical therapy.
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