Remodeling of Adhesion Network within Cancer Spheroids via Cell–Polymer Interaction

3D
spheroids are considered as the improved in vitro model to mimic the distinct arrangements of the cells in
vivo. To date, low-attachment surfaces have been most widely
used to induce the spontaneous aggregation of cells in suspension
by simply tuning the relative strength of the cell–cell adhesion
over cell–substrate adhesion. However, aggregating cancer cells
into 3D clusters should mean more than just adjoining the cells in
the physical proximity. The tumor cell functionality is strongly affected
by the adhesion networks between cancer cells and extracellular matrix
(ECM). Here, we performed an in-depth analysis of how the nonmetastatic
breast cancer cells (MCF7) can be transformed to gain invasive phenotypes
through compact aggregation into 3D spheroids on a functional polymer
film surface, poly­(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane)
(pV4D4). By comparing the adhesion networks
and invasion dynamics between 3D spheroids cultured on the pV4D4 surface
with those cultured on conventional ultra-low-attachment (ULA) dishes,
we report that only spheroids on the pV4D4 display active and sporadic
cell–surface binding activities via dynamic protrusions, which
correlates strongly with an increase in integrin β1. Moreover,
localized laminin expression at the core of the pV4D4-cultured spheroids
confirms the prominence of the intimate integrin–laminin interactions
prompted by the exposure to pV4D4. This study suggests that structurally
and functionally dissimilar 3D spheroids can be generated from the
same type of cells on the surfaces of different physicochemical properties
without any chemical treatment or genetic manipulation.