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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1990-5-3
pubmed:abstractText
We showed previously that insulin-like growth factor I (IGF-I) is detectable in small cell lung cancer (SCLC) tumor biopsies and cell lines and that recombinant human IGF-I stimulates DNA synthesis in SCLC cells. Here we report further studies on the role of IGF-I in 2 SCLC cell lines: HC12, classic; and ICR-SC17, variant. Immunoreactive IGF-I was detected in medium conditioned by HC12 but not ICR-SC17. Both HC12 and ICR-SC17 bound IGF-I with 100-fold greater affinity than insulin. Scatchard analysis revealed two classes of IGF-I binding site of high (Kd 0.1 nM, n = 2,300) and lower (Kd 3 nM, n = 28,000) affinity. In both cell lines [3H]thymidine incorporation was enhanced by recombinant human IGF-I, 100-1000 ng/ml. ICR-SC17 also showed growth enhancement as measured by increase in cell numbers. There was no response in HC12, probably due to endogenous IGF-I production. 125I-IGF-I binding and basal and IGF-I-stimulated mitogenesis were inhibited by monoclonal antibodies to IGF-I (SM1.20B, SM1.25) or the type I IGF receptor alpha IR3 but not an isotypic control monoclonal antibody. Antiproliferative effects were manifest in [3H]thymidine incorporation assays in serum-free conditions and growth of serum-supplemented liquid cultures. We also tested fresh or newly cultured tumor cells obtained by fine needle aspiration of metastases in three previously untreated and four relapsed patients with SCLC. IGF-I binding sites were demonstrable on fresh SCLC cells, and specific binding was inhibited by SM1.20B. All seven samples showed stimulation of [3H]thymidine incorporation in the presence of recombinant human IGF-I, 100-500 ng/ml. As in cultured cells, basal and IGF-I-stimulated DNA synthesis was inhibited by monoclonal antibodies SM1.20B, SM1.25, and alpha IR3 but not the isotypic control. These results confirm the findings of previous studies and suggest that IGF-I can function as an autocrine growth factor in SCLC in vitro and possibly also in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2511-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells.
pubmed:affiliation
Section of Medicine Research Laboratories, Institute of Cancer Research, Belmont, Surrey, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't