Fig. 7. Inhibition of
v-integrins blocks epimorphin-mediated epithelial morphogenesis. (A) Extracellular epimorphin stimulates luminal or branching morphogenesis in HMECs, depending upon mode of presentation. In suspension culture HMECs form clearly rounded spherical aggregates after 24 hours (see top two micrographs). Adenovirus carrying signal peptide-tagged epimorphin (Av-SE) was added to the suspension culture for the final two hours (cells form well-packed aggregate and Av-SE infects only outer cells in the aggregate) for polar presentation, or first 2 hours (when cells remain single and Av-SE infects all cells in the aggregate) for apolar presentation; embedding of the resultant cell aggregates in 3D collagen gels produced branching or luminal morphogenesis, respectively. Bar, 50 µm. Blot on the right shows HMECs treated with Av-SE producing 37 kDa glycosylated epimorphin. (B) Antibodies against
v-integrin block both branching and luminal morphogenesis. Data are the mean ± s.d., n=3. The phenotypic appearance (branching or luminal) was evaluated as described previously (Hirai et al., 1998).