Linked Life Data

18537183

Source:http://linkedlifedata.com/resource/pubmed/id/18537183

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-7-10
pubmed:abstractText
The protumorigenic insulin-like growth factor (IGF)-II is highly expressed in a significant fraction of human hepatocellular carcinomas (HCC). However, a functional dissection that clarifies the contribution of IGF-II-binding receptors in tumor progression and a respective molecular characterization of IGF-II signaling has not been performed. Therefore, expression of IGF-II and its receptors IGF-receptor type I (IGF-IR) and insulin receptor (IR) was efficiently blocked using small interfering RNA (siRNA) in HCC cells. Despite functional IR-signaling, oncogenic IGF-II effects such as tumor cell viability, proliferation, and anti-apoptosis were solely transmitted by IGF-IR. Although IGF-II signaling was previously not described in the context of HCC cell migration, the IGF-II-dependent expression profile displayed a high percentage of genes involved in cell motility and adhesion. Indeed, IGF-II overexpression promoted HCC cell migration, especially in synergy with hepatocyte growth factor (HGF). The therapeutic relevance of IGF-II/IGF-IR signaling was tested in vitro and in a murine xenograft transplantation model using the IGF-IR inhibitor picropodophyllin (PPP). IGF-IR inhibition by small molecule treatment efficiently reduced IGF-II-dependent signaling and all protumorigenic properties of the IGF-II/IGF-IR pathway. CONCLUSION: In human HCC cells, IGF-IR but not IR is involved in oncogenic IGF-II signaling. Autocrine stimulation of IGF-II induces HCC motility by integration of paracrine signals for full malignant competence. Thus, activation of IGF-II/IGF-IR signaling is likely a progression switch selected by function that promotes tumor cell dissemination and aggressive tumor behavior.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
146-56
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18537183-Animals, pubmed-meshheading:18537183-Autocrine Communication, pubmed-meshheading:18537183-Carcinoma, Hepatocellular, pubmed-meshheading:18537183-Cell Movement, pubmed-meshheading:18537183-Disease Progression, pubmed-meshheading:18537183-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18537183-Humans, pubmed-meshheading:18537183-Insulin-Like Growth Factor II, pubmed-meshheading:18537183-Liver Neoplasms, pubmed-meshheading:18537183-Mice, pubmed-meshheading:18537183-Neoplasm Invasiveness, pubmed-meshheading:18537183-Neoplasm Transplantation, pubmed-meshheading:18537183-Podophyllotoxin, pubmed-meshheading:18537183-Protein Kinase Inhibitors, pubmed-meshheading:18537183-Receptor, IGF Type 1, pubmed-meshheading:18537183-Signal Transduction, pubmed-meshheading:18537183-Transplantation, Heterologous, pubmed-meshheading:18537183-Tumor Cells, Cultured, pubmed-meshheading:18537183-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a progression step in human hepatocarcinogenesis.
pubmed:affiliation
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't