Figure S1 from Breast Cancer Metastatic Dormancy and Relapse: an Enigma of Microenvironment(s)

Figure S1. Current experimental models to study breast cancer metastatic dormancy. (a) Different pairs of cell lines are used to study breast cancer dormancy in vitro. Both 4T07 and D2OR cells remain dormant in the secondary site after spontaneous metastasis. In contrast, 4T1 and D2A1, their corresponding counterparts, form overt metastases. (b) A simplistic representation of the in vitro 3D culture systems’ components as described in different studies. ECM-like components such as collagen and laminin among other factors (fibronectin, heparin, TGFB and others) have been included in different culture systems to recapitulate the native microenvironments. In addition, these culture systems include various cell types to be co-cultured with the cancer cells such as stromal and endothelial cells. These culture systems allowed studying the dormancy phase and the consequent switch to a proliferative state. (c) The transgenic MMTV-Neu mouse model has been leveraged to study breast cancer dormancy in vivo. This HER2+ subtype model develops spontaneous mammary tumors, and early DTCs can be detected in the lungs and the bone marrow during the early stages of tumorigenesis such as ADH and DCIS, around 9 weeks of age, hence before the invasive stage onset which is typically seen around 23-30 weeks of age. The endpoint stage is characterized by the detection of macrometastases. However, whether metastases originate from early or late DTCs or both is still an open question.