Linked Life Data

20190463

Source:http://linkedlifedata.com/resource/pubmed/id/20190463

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-3-1
pubmed:abstractText
Tumor progression is a complex process that involves the interaction of cancer cells with the cancer-surrounding stromal cells. The cancer stroma influences the cancer cell growth and metastatic potential. The EGF family growth factor HB-EGF is synthesized in cancer cells and plays pivotal roles in oncogenic transformation and tumor progression, but the contribution of HB-EGF expressed in tumor stromal cells to tumor growth remains unclear. In the present study, we found that HB-EGF was expressed in host-derived cancer stromal cells in xenograft and allograft mouse tumor models. CRM197 is a specific inhibitor of human HB-EGF that has no effect on mouse HB-EGF. To elucidate whether host-derived stromal HB-EGF contributes to tumor growth, we generated knock-in mice expressing a CRM197-inhibitable humanized mutant form of HB-EGF. Administration of CRM197 to humanized knock-in mice that were bearing tumors derived from human or mouse cancer cells revealed that inhibition of host-derived stromal HB-EGF by CRM197 significantly reduced tumor growth. These results suggest that HB-EGF in the cancer-associated stroma plays a significant role for tumor growth, and that the HB-EGF derived from the stroma, as well as that expressed by cancer cells, is a potential target for cancer therapy. The present results also suggest that the humanized HB-EGF knock-in mice could be utilized for pathophysiological studies of HB-EGF as well as the development of therapeutic strategies targeting HB-EGF.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1347-3700
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3-13
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Humanized gene replacement in mice reveals the contribution of cancer stroma-derived HB-EGF to tumor growth.
pubmed:affiliation
Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't