Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7193
pubmed:dateCreated
2008-5-15
pubmed:abstractText
The vasculature of solid tumours is morphologically aberrant and characterized by dilated and fragile vessels, intensive vessel sprouting and loss of hierarchical architecture. Constant vessel remodelling leads to spontaneous haemorrhages and increased interstitial fluid pressure in the tumour environment. Tumour-related angiogenesis supports tumour growth and is also a major obstacle for successful immune therapy as it prevents migration of immune effector cells into established tumour parenchyma. The molecular mechanisms for these angiogenic alterations are largely unknown. Here we identify regulator of G-protein signalling 5 (Rgs5) as a master gene responsible for the abnormal tumour vascular morphology in mice. Loss of Rgs5 results in pericyte maturation, vascular normalization and consequent marked reductions in tumour hypoxia and vessel leakiness. These vascular and intratumoral changes enhance influx of immune effector cells into tumour parenchyma and markedly prolong survival of tumour-bearing mice. This is the first demonstration, to our knowledge, of reduced tumour angiogenesis and improved immune therapeutic outcome on loss of a vascular gene function and establishes a previously unrecognized role of G-protein signalling in tumour angiogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
453
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
410-4
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Vascular normalization in Rgs5-deficient tumours promotes immune destruction.
pubmed:affiliation
Western Australian Institute for Medical Research, UWA Centre for Medical Research, Perth, Western Australia 6000, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't