Enhancement of aberrantly modified integrin-mediated cell motility in multicellular tumor spheroids

Abstract

Multicellular tumor spheroids (MTSs) of malignant cells can display cell-cell and cell-matrix interactions, different from monolayer cultures. The objective of the present study was to examine difference in intercellular and cell-matrix interaction between monolayered cultures and spheroid cultures. Expression levels of cell adhesion molecules (CAMs) and epithelial-mesenchymal transition (EMT) signaling molecules in monolayered cells and MTS cells were compared. The motility of single cells dispersed from each culture was evaluated using a live-cell imaging device. The effect of an E-cadherin neutralizing antibody, DECMA, was also compared between the two cultures. Among various CAMs, only E-cadherin was increased in MTSs. The motility of single cells dispersed from MTSs was higher than that from monolayered cells. Compared with monolayered cells, the molecular weight (MW) of β1 integrin was decreased during MTS formation, particularly during the early stage. This notable reduction was maintained when DECMA was used to treat MTSs. Additionally, the expression levels of the EMT signaling molecules Snail and ILK increased more in MTSs than in monolayered cells. The blocking of E-cadherin elicited increased expression levels of EMT molecules and cellular motility only in MTSs. In conclusion, the alteration of E-cadherin expression and presence of low-MW β1 integrin in MTS may enhance cell motility via the upregulation of EMT signaling molecules that may be intensified by blocking E-cadherin.