Interactions occurring between malignant cells and the stromal microenvironment heavily influence tumor progression. We investigated whether this cross-talk affects some molecular and functional aspects specifically correlated with the invasive phenotype of breast tumor cells (i.e. adhesion molecule expression, membrane fluidity, migration) by co-culturing mammary cancer cells exhibiting different degrees of metastatic potential (MDA-MB-231>MCF-7) with fibroblasts isolated from breast healthy skin (normal fibroblasts, NFs) or from breast tumor stroma (cancer-associated fibroblasts, CAFs) in 2D or 3D (nodules) cultures. Confocal immunofluorescence analysis of the epithelial adhesion molecule E-cadherin on frozen nodule sections demonstrated that NFs and CAFs, respectively, induced or inhibited its expression in MCF-7 cells. An increase in the mesenchymal adhesion protein N-cadherin was observed in CAFs, but not in NFs, as a result of the interaction with both kinds of cancer cells. CAFs, in turn, promoted N-cadherin up-regulation in MDA-MB-231 cells and its de novo expression in MCF-7 cells. Beyond promotion of “cadherin switching”, another sign of the CAF-triggered epithelial-mesenchymal transition (EMT) was the induction of vimentin expression in MCF-7 cells. Plasma membrane labeling of monolayer cultures with the fluorescent probe Laurdan showed an enhancement of the membrane fluidity in cancer cells co-cultured with NFs or CAFs. An increase in lipid packing density of fibroblast membranes was promoted by MCF-7 cells. Time-lapsed cell tracking analysis of mammary cancer cells co-cultured with NFs or CAFs revealed an enhancement of tumor cell migration velocity, even with a marked increase in the directness induced by CAFs.Our results demonstrate a reciprocal influence of mammary cancer and fibroblasts on various adhesiveness/invasiveness features. Notably, CAFs' ability to promote EMT, reduction of cell adhesion, increase in membrane fluidity, and migration velocity and directness in mammary cancer cells can be viewed as an overall progression- and invasion-promoting effect.

Background: The aim of this study was to compare outcomes of immediate prosthetic breast reconstruction (IPBR) using traditional submuscular (SM) positioning of implants versus prepectoral (PP) positioning of micropolyurethane-foam-coated implants (microthane) without further coverage. Methods: We retrospectively reviewed the medical records of breast cancer patients treated by nipple-sparing mastectomy (NSM) and IPBR in our institution during the two-year period from January 2018 to December 2019. Patients were divided into two groups based on the plane of implant placement: SM versus PP. Results: 177 patients who received IPBR after NSM were included in the study; implants were positioned in a SM plane in 95 patients and in a PP plane in 82 patients. The two cohorts were similar for mean age (44 years and 47 years in the SM and PP groups, respectively) and follow-up (20 months and 16 months, respectively). The mean operative time was 70 min shorter in the PP group. No significant differences were observed in length of hospital stay or overall major complication rates. Statistically significant advantages were observed in the PP group in terms of aesthetic results, chronic pain, shoulder dysfunction, and skin sensibility (p < 0.05), as well as a trend of better outcomes for sports activity and sexual/relationship life. Cost analysis revealed that PP-IPBR was also economically advantageous over SM-IPBR. Conclusions: Our preliminary experience seems to confirm that PP positioning of a polyurethane-coated implant is a safe, reliable and effective method to perform IPBR after NSM.

The influence of cell membrane fluidity on cancer progression has been established in different solid tumors. We previously reported that “cancer-associated fibroblasts” (CAFs) induced epithelial-mesenchymal transition and increased cell membrane fluidity and migration in poorly (MCF-7) and highly invasive (MDA-MB-231) breast cancer cells. We also found that the membrane fluidity regulating enzyme stearoyl-CoA desaturase 1 (SCD1) was upregulated in tumor cells co-cultured with CAFs and established its essential role for both intrinsic and CAF-driven tumor cell motility. Here, we further explored the mechanisms involved in the SCD1-based modulation of breast cancer cell migration and investigated the role of the other human SCD isoform, SCD5. We showed that the addition of oleic acid, the main SCD1 product, nullified the inhibitory effects produced on MCF-7 and MDA-MB-231 cell migration by SCD1 depletion (pharmacological or siRNA-based). Conversely, SCD5 seemed not involved in the regulation of cancer cell motility. Interestingly, a clear induction of necrosis was observed as a result of the depletion of SCD5 in MCF-7 cells, where the expression of SCD5 was found to be upregulated by CAFs. The necrotic effect was rescued by a 48-h treatment of cells with oleic acid. These results provide further insights in understanding the role of SCD1 in both intrinsic and CAF-stimulated mammary tumor cell migration, unveiling the metabolic basis of this desaturase-triggered effect. Moreover, our data suggest the ability of CAFs to promote the maintenance of tumor cell survival by the induction of SCD5 levels.

Conservative surgery has become a well-established alternative to mastectomy in the treatment of breast cancer. However, in case of larger lesions or small-size breasts, the removal of adequate volumes of breast tissue to achieve tumor-free margins and reduce the risk of local relapse may compromise the cosmetic outcome, causing unpleasant results. In order to address this issue, new surgical techniques, so-called oncoplastic techniques, have been introduced in recent years to optimize the efficacy of conservative surgery both in terms of local control and cosmetic results. This article discusses the indications, advantages, and limitations of these techniques and their results in terms of local recurrence and overall survival.