A Lamb1Dendra2 Mouse Model Reveals Basement Membrane-Producing Origins and Dynamics in PyMT Breast Tumors

The basement membrane (BM) is crucial for tissue organization and myoepithelial cells are key producers of BM components in the healthy mammary gland. Interestingly, these BMproducing cells are no longer present in advanced mammary tumors, yet those tumors are surrounded by BMs. To study the origin and dynamics of the tumor BM, we developed a laminin beta1-Dendra2 mouse model. Using the PyMT model of spontaneous breast cancer and transplantation approaches in combination with intravital imaging, we identify that the tumor BM is not a remnant of the healthy mammary epithelium BM, but instead, that epithelial breast cancer cells synthesize and organize their own BM autonomously. Additionally, tumor-infiltrating endothelial cells produce and organize their own laminin beta1, thereby assembling the BM around newly formed tumor vasculature. Although both types of BMs are continuously renewed, the disassembly rate of the blood vessel BM is faster than its counterpart around tumor lobes. Importantly, the counteracting assembly of the BMs at both sites is temporarily and locally heterogeneous, leading to local discontinuity of the BM. Taken together, our new photo-switchable Dendra2-tagged laminin beta1 mouse model reveals BM-producing sources and draws a new paradigm for BM dynamics and function in PyMT mammary tumors.