Role of cell-to-cell communication in guiding breast cancer cell physiology

Abstract

The ability of cells to communicate constitutes an important characteristic of all multi- cellular organisms. Cells participate in a continuous relay of information between their environment and other cells. These connections and the relayed information (exchange of biomolecules) influence how cells grow and function, with some literature suggesting that cell-to-cell communication may play a role in tumour progression. For instance, cancer cells interacting with stromal cells are believed to lead to the remodelling of the extracellular matrix to promote invasion and metastasis. The development of metastasis has been implicated as a major cause of the worsening of prognosis for the majority of cancer patients. Breast cancer is only lethal when primary tumours travel to secondary sites or organs and impede their normal function, for example, when metastatic breast cancer invades the lungs or brain and results in death. Bearing in mind that breast cancer is the most prevalent form of cancer affecting women, preventing this complex process could impact many lives. These interactions are not limited to neoplastic cells communicating with normal cells, and vice versa, but also between different neoplastic cells as well. The methods and mechanisms of action have not yet been characterized. This presents an opportunity in cancer studies/therapeutic development, in that targeting a non-metastatic cell capable of influencing a metastatic cancer cells’ behaviour (or vice versa) would not only present a single target to impact metastasis, but also the opportunity to impact two neoplastic cell populations with one therapeutic target. In this study, we investigated intercellular crosstalk between breast cancer cell lines and the possible resulting effects. The data generated shows that communication does take place between the different breast cancer cell lines. We observed that the biomolecules communicated from the metastatic MDA-MB-231 cell line triggered cell cycle exit and eventual apoptosis within the non-metastatic BT20 cell line. Additionally, we confirmed that biomolecule transfer occurs between donor and recipient cell within a two- and three-dimensional culture setting via the inducible colour switch system.