Multidimensional Cellular Micro-Compartments to Model Invasive Lobular Carcinoma Dormancy
Abstract:
Invasive lobular carcinoma (ILC) accounts for 10-15% of breast cancers. Despite favorable responses to anti-estrogen therapy, the dissemination of cancer cells and resistance to therapies are significant risks for patients with ILC. Late recurrences are prevalent in ILC, suggesting that disseminated tumor cell dormancy may be a mechanism preceding their late overt growth into metastatic lesions. Herein, we investigated the relationship between anti-estrogen resistance and dormancy through multidimensional in vitro models. The bioengineered platforms recapitulated the morphological characteristics of ILC and highlighted its distinction from invasive ductal carcinoma. Inducing a dormant phenotype revealed epigenetic changes and enhanced chemical and mechanical sensing of anti-estrogen-resistant ILC cells to the substrate surface, with p27Kip1 signaling playing a central role. We propose this platform as a high-throughput method to investigate the propensity of dormancy and its manifestation via a simplified and expedited approach.
