TY - JOUR
T1 - Glioma migration can be blocked by nontoxic inhibitors of myosin II
AU - Gillespie, G. Yancey
AU - Soroceanu, Liliana
AU - Manning, Timothy J.
AU - Gladson, Candece L.
AU - Rosenfeld, Steven S.
PY - 1999/5/1
Y1 - 1999/5/1
N2 - Anaplastic gliomas are infiltrative tumors, and their ability to migrate through normal brain contributes to their highly malignant behavior. Invasion of brain requires cell motility, which in turn depends on the activity of the cytoskeleton. A cytoskeletal component central to this process is myosin II, the cytoplasmic analogue of smooth and skeletal muscle myosin. Myosin II activity is regulated by file enzyme myosin light chain kinase, which activates myosin II by phosphorylating it on its regulatory light chain. We have investigated the role of myosin II in glioma motility and invasiveness by examining the effects of two inhibitors of myosin light chain kinase, ML7 and KT5926. Both drugs are potent inhibitors of both glioma motility, as measured by a scrape motility assay, and an in vitro haptotaxis assay. The inhibition of in vitro haptotaxis follows the dose-response relationship expected for competitive inhibition of myosin light chain kinase by these drugs and is seen at drug concentrations that are nontoxic. These results highlight the important role that myosin II contributes to glioma invasiveness and suggest that it may serve as a target in future strategies at blocking invasion by these tumors.
AB - Anaplastic gliomas are infiltrative tumors, and their ability to migrate through normal brain contributes to their highly malignant behavior. Invasion of brain requires cell motility, which in turn depends on the activity of the cytoskeleton. A cytoskeletal component central to this process is myosin II, the cytoplasmic analogue of smooth and skeletal muscle myosin. Myosin II activity is regulated by file enzyme myosin light chain kinase, which activates myosin II by phosphorylating it on its regulatory light chain. We have investigated the role of myosin II in glioma motility and invasiveness by examining the effects of two inhibitors of myosin light chain kinase, ML7 and KT5926. Both drugs are potent inhibitors of both glioma motility, as measured by a scrape motility assay, and an in vitro haptotaxis assay. The inhibition of in vitro haptotaxis follows the dose-response relationship expected for competitive inhibition of myosin light chain kinase by these drugs and is seen at drug concentrations that are nontoxic. These results highlight the important role that myosin II contributes to glioma invasiveness and suggest that it may serve as a target in future strategies at blocking invasion by these tumors.
UR - http://www.scopus.com/inward/record.url?scp=0033135022&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033135022&partnerID=8YFLogxK
M3 - Article
C2 - 10232591
AN - SCOPUS:0033135022
SN - 0008-5472
VL - 59
SP - 2076
EP - 2082
JO - Cancer research
JF - Cancer research
IS - 9
ER -