Abstract 2138: Understanding the microenvironment contribution to ductal carcinoma in situ transition to invasiveness in breast cancer

Abstract

Abstract Breast cancer (BC) is thought to arise from the linear evolution of begins ductal carcinoma in situ (DCIS) to the invasive ductal carcinoma (IDC). DCIS is a poorly understood disease. Diagnosis of DCIS is increasing in the last few years. All DCIS are usually treated, however only 40% of them will progress to IDC if left untreated. Therefore, the challenge in the clinical control of the DCIS is to identify the individual patient risk to develop IDC and apply an adequate treatment and/or follow up. Moreover, microenvironmental factors including neuronal factors have been related to the initiation and progression of breast cancer. For this reason, we are studying how factors related to the nervous system regulate the transition from DCIS to IDC. Our objective is to increase the molecular understanding of the DCIS and its surrounding microenvironment. For this purpose we used a BC progression to invasiveness in vitro model using MCF10A as healthy cell line, MCF10DCIS as mild-aggressive/ DCIS cell line and MCF10A-T as invasive/IDC cell line. First of all, we analyzed the expression of several neural related genes that we have previously described to be associated with breast cancer progression and invasion in our DCIS model. We found that netrin 1 (NTN1) and its receptor UNC5A are upregulated in MCF10DCIS and inhibited in MCF10AT both at the genetic and protein level. In addition, treatment with NTN1 in in vitro 2D and 3D assays reduced epithelial - mesenchymal transition (EMT) markers in MCF10AT. Hence, our results suggest that NTN1 via its receptor UNC5A could be negative regulators of the progression to invasiveness in DCIS. Moreover, in our model, semaphorin 3F (SEMA3F) as well as its receptors, neuropilin 1 (NRP1) and neuropilin 2 (NRP2), are downregulated in MCF10DCIS at the genetic and protein level. Furthermore, we detected that treatment of MCF10DCIS with SEMA3F resulted in an up-regulation of EMT genes. Therefore, SEMA3F and its receptors NRP1 and NRP2 could be pro-invasive elements in the transition of DCIS to IDC. Our results suggest that NTN1 and UNC5A could be considered as good prognosis indicators meanwhile SEMA3F and its receptors expression in DCIS would be indicators of poor prognosis. All these results will contribute to a better knowledge of the DCIS phase in BC, to describe new therapeutical approaches and also to properly classify the risk of progression of each DCIS lesion. Citation Format: Núria Moragas, Leire Recalde-Percaz, Aleix Noguera-Castells, Patricia Fernandez-Nogueira, Mario Mancino, Pedro Gascón, Gemma Fuster. Understanding the microenvironment contribution to ductal carcinoma in situ transition to invasiveness in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2138.