(282g) Invited Speaker: Engineered Microenvironments to Study Breast Cancer Progression
3D organoids with controlled microenvironments using a variety of cancer cell lines and primary patient-derived cells. Without any external stimulus, large organoids develop three key hallmarks of DCIS observed in vivo: increasing organoid size drives hypoxia and metabolic stress; heterogeneous tumor cells spontaneously emerge; and peripheral cells begin to migrate from the parent tumor. A tangible advantage of size controlled microwells is the ability to precisely and reproducibly study how the hypoxic microenvironment induces tumor migration in real time in the same cell population and in isolation from non-tumor cells present in vivo, providing unique opportunity to define tumor-intrinsic mechanisms of transition from non-invasive to invasive phenotypes.
In another study, we have developed collagen-mimetic hydrogels and engineered in vitro microenvironments to study role of benign calcium oxalate vs. malignant hydroxyapatitelike microcalcifications (MCs) in non-invasive to invasive disease progression. A tangible advantage of collagen-mimetic hydrogels is precise control over composition of benign oxalate-like and malignant hydroxyapatite-like MCs. We have shown that our model can
recapitulate clinically observed induction of invasive as well as bone-like phenotypes in non-invasive human DCIS and IDC cells.
Overall, engineered controlled microenvironments can advance our knowledge of various microenvironmental factors such as hypoxic tumor secretome or MCs in breast cancer progression.