Combined Interaction of Cellular and Extracellular Components Causes Genetic Cascade Activation in Breast Cancer Metastasis

Abstract

Breast cancer (BC) consists of malignant cells as well as surrounding nonmalignant cells – fibroblasts, macrophages, endothelial cells, lymphocytes, neutrophils, mesenchymal stem cells, and extracellular matrix (ECM). This surrounding stroma is referred to as the breast tumor microenvironment (BTME). The components of BTME interact with cancerous breast cells for the promotion of BC. The reciprocal cross talk between BTME and neoplastic breast cells, through the secretion of chemicals, growth factors, and chemokines, may lead to cell proliferation, migration, metastasis as well as immune response suppression. Multiple genetic loci, in association with stromal components, are linked to immunological stimuli to induce BC in ductal cells. These genes participate in tumor activation pathways and promote carcinogenesis via fibroblast, leukocyte, and endothelial-cell-mediated responses. The collaborative effect of the cellular components and BTME-associated genes plays vital role in tumor initiation and metastasis of breast cells. This process involves genes which cause degenerative changes in ECM leading to epithelial-mesenchymal transitions, which finally causes metastatic BC. This shows that metastatic BC results from combined activation of different cellular and extracellular components, and their activity is primarily controlled by activation of the genetic cascade. These components work simultaneously to cause metastatic BC.