An ex vivo co-culture model system to evaluate stromal-epithelial interactions in breast cancer

摘要

Breast cancer is the most commonly diagnosed cancer among women worldwide. High breast cancer incidence and mortality rates, especially in obese patients, emphasize the need for a better biological understanding of this disease. Previous studies provide substantial evidence for a vital role of the local extracellular environment in multiple steps of tumor progression, including proliferation and invasion. Current evidence supports the role of adipocytes as an endocrine organ, which produces steroid hormones, pro-inflammatory cytokines and adipokines, such as leptin. To further define the role of the mammary microenvironment on tumorigenesis, we have developed an adipose-tumor epithelial cell co-culture system designed to reproduce the in vivo mammary environment. We validate this model through use of coherent anti-Stokes Raman scattering (CARS) microscopy, a label-free vibrational imaging technique. CARS analysis demonstrates the sustained viability of the adipocytes, and that mammary cancer cell morphology parallels that of tumors in vivo. Also, characterized was the influence of mammary adipose tissue on tumor cell growth and migration. Adipose tissue co-cultured with mammary tumor epithelial cells, in the absence of any serum or supplemental growth factors, resulted in substantial increases in growth and migration of tumor cells. In conclusion, this novel co-culture system provides an ideal model to study epithelial-stromal interactions in the mammary gland. Understanding the relationship between adipose tissue, the most abundant and least studied component of the breast stroma and tumor epithelial cells is critical to clarifying the influence of obesity on the development, progression and prognosis of breast cancer. What's new? Being overweight increases your risk of all kinds of health problems, including cancer, although no one has demonstrated precisely what causes the risk. To investigate the interaction between fat cells and breast tumors, the authors developed a unique co-culture system that mimics the tumor environment in a living body. Fat cells surround the mammary gland in great abundance, yet they remain one of the least-studied types of cell in the tumor environment. By culturing tumor cells together with fat cells, the authors demonstrated that the fat cells stimulated tumor growth. The novel culture design provides a valuable new tool for looking at interactions among the different cell types present in the living system.