Photocrosslinked alginate gels for analysis of stromal cell behavior in tumors

The stromal compartment of the normal breast microenvironment is abundant in adipose progenitor cells. These cells experience differential mechanical cues during mammary tumorigenesis; however, it is largely unknown whether tumor-mediated reduction in extracellular matrix (ECM) compliance alters the behavior of adipose progenitor cells. To investigate this possible relationship we have developed an artificial ECM whose elastic moduli may be readily adjusted to mimic the compliance of normal and cancerous breast tissue. More specifically, alginate hydrogels were covalently modified with RGD-adhesion peptides and photocrosslinkable side chains to allow for control over cellular interactions and compliance of these materials, respectively. We have utilized these materials to encapsulate 3T3-L1 mouse preadipocytes and analyze their proliferation and differentiation behavior as a function of tumor-mediated microenvironmental stiffness. Results obtained by these studies may help to elucidate the role of physical cues in modulating stromal cell behavior in the mammary tumor microenvironment and may ultimately lead to a better understanding of breast tumorigenesis.