Abstract 3152: Integrin {alpha}6{beta}1 dependent collective cell migration in prostate cancer metastasis

In this study, we optimized the growth and retrieval of tumor cells from 3-dimensional matrigel cultures, to determine the role of integrin α6β1, α6pβ1 and α3β1 in DU145 prostate tumor cell collective migration. The DU145 prostate tumor cells embedded in growth factor reduced matrigel, grew robust networks within 24 hours and contained extensive branching structures. The network formation was shown to be dependent on integrin α6β1 expression as determined by specific knockdown of α6β1 over a 24 hour period using 25nM siRNA targeting. Interestingly, the knockdown of α3β1 integrin had no observable effect on the networks. The networks produced by the DU145 cells contained pericellular proteolysis activity along the branches of collective cells as well as at the leading tips of the branches. Laminin 332, its receptor integrin α6β1, and uPAR co-localized on the membranes between cells traveling collectively. Induced production of integrin α6pβ1 increased branching network formation, while blockage of integrin α6pβ1 production impaired collective migration via reduced network formation. Taken together, these observations suggest that collective cell migration through tubulogenesis requires cell adhesion to laminin via integrin α6β1 and production of the α6pβ1 structural variant facilitates this process. Ongoing work is using the model to identify candidate molecular effectors of tubulogenesis as well as pharmacological approaches to block the process and prev...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Biology Source Type: research