In:
Journal of Cell Science, The Company of Biologists
Abstract:
Members of the Hedgehog (Hh) family of morphogens play critical roles in development, but are also involved in the progression of certain types of cancer. Despite being synthesized as hydrophobic dually lipid modified molecules, and thus strongly membrane-associated, Hh ligands are able to spread through tissue and act on target cells several cell diameters away. Various mechanism that mediate Hh release have been discussed in recent years, however, little is known about dispersion of this ligand from cancer cells. Using coculture models in conjunction with a newly developed reporter system, we were able to show that different members of the ADAM family of metalloproteases strongly contribute to the release of endogenous, bioactive Hh from pancreatic cancer cells, but that this solubilization decreases the potency of cancer cells to signal to adjacent stromal cells in direct coculture models. These findings imply that under certain conditions, cancer cell-tethered Hh molecules are the more potent signaling activators and that retaining Hh on the surface of cancer cells can unexpectedly increase the effective signaling range of this ligand depending on tissue context.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2014
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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