Obesity increases the risk and worsens the prognosis for
breast cancer due, in part, to altered adipose stromal cell (ASC) behavior. Whether ASCs from obese individuals increase migration of
breast cancer cells relative to their lean counterparts, however, remains unclear. To test this connection, multicellular spheroids composed of MCF10A-derived tumor cell lines of varying malignant potential and lean or obese ASCs were embedded into
collagen scaffolds mimicking the elastic moduli of interstitial breast adipose tissue. Confocal image analysis suggests that
tumor cells alone migrate insignificantly under these conditions. However, direct cell-cell contact with either lean or obese ASCs enables them to migrate collectively, whereby obese ASCs activate
tumor cell migration more effectively than their lean counterparts. Time-resolved optical coherence tomography (OCT) imaging suggests that obese ASCs facilitate
tumor cell migration by mediating contraction of local
collagen fibers.
Matrix metalloproteinase (
MMP)-dependent proteolytic activity significantly contributes to ASC-mediated
tumor cell invasion and
collagen deformation. However, ASC contractility is also important, as co-inhibition of both
MMPs and contractility is necessary to completely abrogate ASC-mediated
tumor cell migration. These findings imply that
obesity-mediated changes of ASC phenotype may impact
tumor cell migration and invasion with potential implications for
breast cancer malignancy in obese patients.