BackgroundThe function of preadipocytes in the progression of early stage breast cancer has not been fully elucidated at the molecular level. To delineate the role of preadipocytes in breast cancer progression, we investigated the cross-talk between human breast ductal carcinoma in situ (DCIS) cells and preadipocytes with both an in vitro culture and xenograft tumor model.MethodsGFP or RFP was transduced into human DCIS cell line MCF10DCIS.com cells or preadipocytes using lentivirus. Cell sorter was used to separate pure, viable populations of GFP- or RFP-transduced cells. Cell viability and proliferation was assessed by crystal violet assays and cell migration and invasion capability was assayed by the transwell strategy. Gene and protein levels were measured by western blot, RT-PCR and immunostaining. Adipokines and cytokines were quantified using ELISA. Human tumor xenografts in a nude mice model were used. Ultrasound imaging of tumors was performed to evaluate the therapeutic potential of a IL-6 neutralizing antibody.ResultsIn the co-culture system with the MCF10DCIS.com and preadipocytes, MCF10DCIS.com proliferation, migration and invasion were enhanced by preadipocytes. Preadipocytes exhibited in an increased IL-6 secretion and cancer-associated fibroblast markers expression, FSP1 and α-SMC in co-culture with MCF10DCIS.com or in MCF10DCIS.com conditioned media, whereas the adipocyte differentiation capacity was suppressed by co-culture with MCF10DCIS.com. A neutralizing antibody of IL-6 or IL-6R suppressed the promotion of MCF10DCIS.com proliferation and migration by co-culture with preadipocytes. In the xenograft tumor model, the tumor growth of MCF10DCIS.com was enhanced by the co-injection of preadipocytes, and the administration of IL-6 neutralizing antibodies resulted in potent effects on tumor inhibition.ConclusionsOur findings suggest that IL-6-mediated cross-talk between preadipocytes and breast DCIS cells can promote the progression of early stage breast cancer. Therefore, blocking IL-6 signaling might be a potential therapeutic strategy for breast DCIS characterized by pathological IL-6 overproduction.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0867-3) contains supplementary material, which is available to authorized users.
Objective. Higher breast density is a strong, independent risk factor for breast cancer. Breast density varies by age, ethnicity, and geographic area although dense breast tissue has been associated with younger age and premenopausal status. The relationship between breast density and age in women in the United Arab Emirates (UAE) has not been determined. This study evaluated breast density in the UAE population and its relationship with age. Methods. Women participating in the national cancer screening program from August 2015 to May 2018 who underwent screening mammography were included. Breast parenchymal density was classified according to the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) from category a (almost entirely fatty) through d (extremely dense). Subjects were divided into six age groups, and the association between age and breast density was evaluated. Results. Of the 4911 women included, 1604 (32.7%), 2149 (43.8%), 1055 (21.5%), and 103 (2.1%) were classified as having categories a–d breast density, respectively. A significant negative correlation was observed between age and breast density category (p<0.001). Women of mean age 44 ± 7 years had the highest breast density, whereas those of mean age 56 ± 14 years had the lowest breast density. Comparisons of Emirati women with Lebanese and Western women showed that breast density was lower in Emirati women than in the other populations. Conclusions. To our knowledge, this is the first study to evaluate the relationship between mammographic breast density and age in UAE women. As in other populations, age was inversely related to breast density, but the proportion of Emirati women with dense breasts was lower than in other populations. Because this study lacked demographic, clinical, and histopathological data, further evaluation is required.
The mechanisms underlying breast cancer progression of ductal carcinoma in situ (DCIS) associated with fatty acids are largely unknown. In the present study, we compared the action of oleic acid (OA) on two human DCIS cell lines, MCF10DCIS.COM (ER/PR/HER2-negative) and SUM225 (HER2 overexpressed). OA led to a significant increase in proliferation, migration, lipid accumulation and the expression of lipogenic proteins, such as SREBP-1, FAS and ACC-1, in MCF10DCIS.COM cells but not SUM225 cells. The ALDHhigh subpopulation analyzed by the ALDEFLUOR assay was approximately 39.2±5.3% of MCF10DCIS.COM cells but was small (3.11±0.9%) in SUM225 cells. We further investigated the different biological action of OA in the distinct ALDHlow and ALDHhigh subpopulations of MCF10DCIS.COM cells. OA led to an increase in the expression of ALDH1A1, ALDH1A2 and ALDH1A3 in MCF10DCIS.COM cells. SREBP-1 and ACC-1 were highly expressed in ALDHhigh cells relative to ALDHlow cells, whereas FAS was higher in ALDHlow cells. In the presence of OA, ALDHhigh cells were more likely to proliferate and migrate and displayed significantly high levels of SREBP-1 and FAS and strong phosphorylation of FAK and AKT relative to ALDHlow cells. This study suggests that OA could be a critical risk factor to promote the proliferation and migration of ALDHhigh cells in DCIS, leading to breast cancer progression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.