Secretion of autocrine growth factors by cultured human lung tumors: Effects on neoplastic lung epithelial cells

Siegfried, Jill M.; Hansen, Suzanne K.; Lawrence, Vickie Y.; Owens, Sara E.

doi:10.1016/s0169-5002(88)80048-5

Cited by 6 publications

(2 citation statements)

References 3 publications

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“…IGF-I has growth-stimulating effects on epithelial and mesenchymal cells in vivo (5,6) and in vitro (7,8) and has been proposed to function as an autocrine or paracrine growth factor in human malignancies including lung tumors (9)(10)(11)(12)(13). Developing lung of the human fetus has also been shown to express high levels of IGF-I mRNA (14).…”

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confidence: 99%

A mitogenic peptide amide encoded within the E peptide domain of the insulin-like growth factor IB prohormone.

Siegfried

Kasprzyk

Treston

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

112

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We have identified an amino acid sequence within the E peptide of the insulin-like growth factor IB (IGF-IB) precursor that is biologically active and designated this peptide insulin-like growth factor IB-(103-124) E1 amide (IBEl). Its existence was predicted by a flanking Gly-Lys-LysLys, a signal sequence for sequential proteolytic cleavage and peptidyl C-terminal amidation. A synthetic analog of the predicted IBE, peptide, designated Y-23-R-NH2, was generated with tyrosine added at position 0. This peptide at 2-20 nM had growth-promoting effects on both normal and malignant human bronchial epithelial cells. Y-23-R-NH2 bound to specific high-affinity receptors (Kd = 2.8 ± 1.4 x 10-11 M) present at 1-2 x 104 binding sites per cell. Ligand binding was not inhibited by recombinant insulin or recombinant IGF-I. Furthermore, a monoclonal antibody antagonist to the IGF-I receptor (aIR3) did not suppress the proliferative response induced by Y-23-R-NH2. In addition, C-terminal amidation was shown to be important in receptor recognition since the free-acid analog of IBE1 (Y-23-R-OH) did not effectively compete for binding and was not a potent agonist of proliferation. Immunoblot analysis of human lung tumor cell line extracts using an antibody raised against Y-23-R-NH2 detected a low molecular mass band of -5 kDa, implying that a protein product is produced that has immunological similarity to IBE1.Extracts of human, mammalian, and avian livers analyzed on an immunoblot with the anti-Y-23-R-NH2 antibody contained proteins of :21 kDa that were specifically recognized by the antiserum and presumably represent an IGF-I precursor molecule. This implies that in species where an IGF-I mRNA with homology to the human IGF-IB E domain has not yet been described, an alternate mRNA must be produced that contains a sequence similar to that of the midportion of the human IGF-IB E domain. Our rmdings demonstrate that IBE1 is a growth factor that mediates its effect through a specific highaffinity receptor and is most likely conserved in many species.

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confidence: 99%

A mitogenic peptide amide encoded within the E peptide domain of the insulin-like growth factor IB prohormone.

Siegfried

Kasprzyk

Treston

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

112

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“…CM from A549 cells has been shown to contain both TGFa-and IGF-I-like peptides at levels of 0.14.5 ng/ml [4,6]. Purified recombinant peptides were used in a clonal assay to demonstrate responsiveness of primary lung tumor cells to peptides at the levels detected in CM (Fig.…”

Section: Resultsmentioning

confidence: 99%

Culture of primary lung tumors using medium conditioned by a lung carcinoma cell line

Siegfried

1989

J of Cellular Biochemistry

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Medium conditioned by the established lung tumor cell line A549 was used as a supplement to culture cells from primary solid lung tumors. Of 36 cases placed into culture, primary cells were obtained in 33 (91.7%). Of 29 cases in which subcultures were attempted, 18 (62.1%) were successful. Nine cell lines have been established by this technique to date. In growth assays, conditioned medium (CM) was found to stimulate both monolayer colony formation and growth in semi-solid medium of cells cultured from primary solid tumors. CM has been found to contain factors with the properties of both transforming growth factor alpha (TGF alpha) and insulin-like growth factor-I (IGF-I). The addition of a combination of these factors as purified peptides to basal medium at levels found in CM (0.1-0.5 ng/ml) stimulated colony formation of lung tumor cells by up to fourfold. These results indicate that secretion of growth factors may be important in tumor growth in vivo, and that use of CM may be a valuable tool for obtaining cultures from primary solid tumors.

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Expression of functional PDGF β receptors in a human large‐cell lung‐carcinoma cell line

Forsberg

Bergh

Westermark

1993

Intl Journal of Cancer

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In this study we have investigated a panel of lung-cancer cell lines, both of small-cell carcinoma and non-small-cell type, for the expression of receptors for platelet-derived growth factor. Although we found mRNA expression for the beta-type receptor on one small-cell and one non-small-cell line and alpha-type receptor mRNA expression on one small-cell-cancer cell line, only the beta receptors of the non-small-cell line (H-157) proved to be functional. Thus, the cell line H-157 displayed specific binding of 125I-PDGF-BB in addition to mRNA expression of the 6-kb transcript for the PDGF beta type receptor. Further evidence for the presence of functional PDGF beta receptors in H-157 cells was obtained from an in vitro kinase assay, which demonstrated a ligand-induced receptor autophosphorylation as well as the phosphorylation of a number of potential substrates associated with the activated receptor.

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Secretion of autocrine growth factors by cultured human lung tumors: Effects on neoplastic lung epithelial cells

Cited by 6 publications

References 3 publications

A mitogenic peptide amide encoded within the E peptide domain of the insulin-like growth factor IB prohormone.

A mitogenic peptide amide encoded within the E peptide domain of the insulin-like growth factor IB prohormone.

Culture of primary lung tumors using medium conditioned by a lung carcinoma cell line

Expression of functional PDGF β receptors in a human large‐cell lung‐carcinoma cell line

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