Figure 4. Dormant breast cancer cells reside in a perivascular niche following dissemination from the primary tumor.

In an in vivo model of tumor cell dormancy, a weakly metastatic breast cancer cell line (T4-2, green) disseminated from the primary tumor and localized to perivascular niches (marked by CD31, red) in the (A) lungs, (B) bone marrow, and (C) brain. The cells are dormant as shown by the absence of the proliferation marker, Ki67. (D) In an organotypic in vitro model of the bone marrow microvasculature, the T4-2 cells remained dormant (Ki67 negative, denoted with white asterisks) when localized next to stable vasculature (further examples in panels ii – iv.), but were induced to a highly proliferative state when localized next to neovascular tips (denoted by T). These proliferative clusters have the potential to become new metastatic lesions. DNA was labeled with Hoechst 33342 (blue). Adapted by permission from Macmillan Publishers Ltd: Nature Cell Biology⁶⁹ copyright 2013.