Stromal Co-Cultivation for Modeling Breast Cancer Dormancy in the Bone Marrow

SIMPLE SUMMARY: Cancer cells travel to far away parts of the body before the original cancer can be detected. Breast cancer cells travel mainly to the bone marrow, where they are kept in a quiet, non-dividing, dormant state for many years by cells and proteins in the bone marrow. These metastatic cancer cells wake up at a steady rate over the years and result in incurable disease. This paper outlines how to study the interactions of cells that live in the bone marrow with cancer cells in the laboratory. We describe how to grow mixtures of a variety of bone marrow-residing cells to generate cell layers upon which cancer cells can be grown. Using this system, we can study their effects on cancer cell growth or dormancy and the biology of the interactions. With this approach, we can study how to either eliminate the cancer cells or prevent them from waking up. ABSTRACT: Cancers metastasize to the bone marrow before primary tumors can be detected. Bone marrow micrometastases are resistant to therapy, and while they are able to remain dormant for decades, they recur steadily and result in incurable metastatic disease. The bone marrow microenvironment maintains the dormancy and chemoresistance of micrometastases through interactions with multiple cell types and through structural and soluble factors. Modeling dormancy in vitro can identify the mechanisms of these interactions. Modeling also identifies mechanisms able to disrupt these interactions or define novel interactions that promote the reawakening of dormant cells. The in vitro modeling of the interactions of cancer cells with various bone marrow elements can generate hypotheses on the mechanisms that control dormancy, treatment resistance and reawakening in vivo. These hypotheses can guide in vivo murine experiments that have high probabilities of succeeding in order to verify in vitro findings while minimizing the use of animals in experiments. This review outlines the existing data on predominant stromal cell types and their use in 2D co-cultures with cancer cells.