Insulin-like growth factor-I is an autocrine regulator for the brain metastatic variant of a human non-small cell lung cell line

Hwang, Chiu Chin; Fang, Kang; Liu, Limin; Shih, Stephen H.

doi:10.1016/0304-3835(95)03845-n

Cited by 9 publications

(10 citation statements)

References 14 publications

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“…In contrast, the growth of H226Br cells was minimally altered (Figure 2). H226Br cells are a variant of H226B cells and were isolated from a brain metastasis in nu/nu mice injected intravenously with H226B cells (Hwang et al, 1995). Relative to H226B, H226Br cells are more tumorigenic in nu/nu mice (Hwang et al, 1995).…”

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confidence: 99%

“…H226Br cells are a variant of H226B cells and were isolated from a brain metastasis in nu/nu mice injected intravenously with H226B cells (Hwang et al, 1995). Relative to H226B, H226Br cells are more tumorigenic in nu/nu mice (Hwang et al, 1995). The levels of IGFBP-6 induced by Ad5CMV-BP6 infection were lower in H226Br cells than in H226B (Figure 1), which could have contributed to the reduced anti-proliferative eect observed in H226Br.…”

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Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells

et al. 2000

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Insulin-like growth factor binding proteins (IGFBPs) are secreted into the extra-cellular matrix and inhibit cell growth through IGF-dependent and -independent mechanisms. In this study, we investigated the role of IGFBP-6, a relatively unexplored member of the IGFBP family, in the proliferation of non-small cell lung cancer (NSCLC) cells. Infection of NSCLC cell lines in vitro with an adenovirus expressing human IGFBP-6 under the control of a CMV promoter (Ad5CMV-BP6) reduced NSCLC cell number through activation of programmed cell death, as shown by cell staining with Hoechst 33342 or DNA end-labeling with bromodeoxyuridine triphosphate. The growth regulatory eect of IGFBP-6 was investigated in vivo by intratumoral injection of Ad5CMV-BP6 in NSCLC xenografts established in nu/nu mice. A single injection of Ad5CMV-BP6 reduced the size of NSCLC xenografts by 45%. These ®ndings indicate that IGFBP-6 is a potent inducer of programmed cell death in cancer cells and support investigations into IGFBP-6 as a potential target in cancer therapeutics. Oncogene (2000) 19, 4432 ± 4436.

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Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells

et al. 2000

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“…H226Br was shown to have a different tumorigenic phenotype from the parental cells, (Hwang et al, 1995). Lung cancer cells studied in this work do not express EGF; instead TGF-ox was found to be expressed as a natural ligand for EGFR (Roth, 1992 Furthermore, the growth of H226Br is inhibited more effectively by TGF-a-specific antibody, indicating that the expressed TGF-ac in H226Br acts as an external autocrine loop regulator in cell growth.…”

Section: Enhanced Egfr Kinase Activity In H226br Cellsmentioning

confidence: 82%

“…Thus, it is interesting to discover that the growth factor autocrine regulation that takes place in the brain may account for tumorigenesis of squamous cells once the blood brain-barrier is overcome. The growth of H226Br has been shown to be regulated by insulin-like growth factor I, which differs from the parental cells (Hwang et al, 1995). Taken together, this work characterising growth factor regulation during malignant transformation provides a better understanding of the spectrum of molecular alteration that occurs during metastasis of brain by human NSCLC cells.…”

Section: Enhanced Egfr Kinase Activity In H226br Cellsmentioning

confidence: 86%

“…Squamous cell carcinoma cells are known for their brain metastasis potential (Schackert et al, 1989;Fidler and Schackert, 1991). The cell line used in this report, H226Br, was derived by intracarotid injection of human NSCLC cells NCI-H226 into athymic BALB/c mice and selected from the developed brain tumour (Hwang et al, 1995). An enhanced TGF-amediated mitogenic response in H226Br cells was observed.…”

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An enhanced and sensitive autocrine stimulation by transforming growth factor-α is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line

Fang

1996

Br J Cancer

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Summary Transforming growth factor-a (TGF-oa)-mediated autocrine regulation in human non-small-cell lung cancer (NSCLC) cells NCI-H226 and its brain metastatic variant H226Br were compared. An enhanced TGFcx-induced dose-dependent mitogenic responsiveness in H226Br cells was observed. Neutralising antibody that binds TGF-a inhibits H226Br cell growth more effectively than NCI-H226 cell growth. Binding assay with 12511 labelled epidermal growth factor (EGF) revealed that H226Br has two types of EGF receptors (EGFRs), whereas the parental cell line, NCI-H226, has only one. H226Br cells contain twice as many EGFRs as H226 cells, as proved by Scatchard analysis and immune kinase assay. Northern analysis indicated that there is more EGFR transcript in H226Br than in NCI-H226, indicating a transcriptional EGFR gene elevation during metastasis progression. The level of accumulated immunoactive TGF-a is lower in the conditioned medium of H226Br than in that of NCI-H226, demonstrating down-regulation of TGF-cc transcript. The accumulated data suggest an elevated and sensitive autocrine modulation by TGF-a and EGFR in immortalising the brain metastatic variant cells that were derived from a human NSCLC squamous cell line.

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Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma

et al. 1998

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Background and Objectives:We have previously shown that insulin-like growth factor (IGF)-responsive murine sarcomas demonstrate inhibition of local and metastatic disease growth when implanted in an IGF-deficient host animal. In this experiment, we tested whether IGF receptor (IGF-R) and ligands were expressed in human primary and metastatic osteosarcomas. Methods: Fifty-two specimens of human osteosarcoma tumor from 48 patients were assayed for IGF-R, IGF-1, and IGF-2 using reverse transcriptase polymerase chain reaction. Results: Twenty-one of 46 tumors analyzed had levels of expression of IGF-R greater than or equal to the positive control cell line. Twenty-seven of 44 expressed levels of IGF-1 greater than or equal to the positive control, as did 21 of 38 cases assayed for IGF-2. No differences were found between 40 primary tumor samples and 12 metastatic lesions in mean levels of IGF-R, IGF-1, or IGF-2. There was a moderately strong correlation between expression of IGF-R and IGF-1, suggesting that autocrine stimulation may be an important mechanism for stimulation of osteosarcoma proliferation. Conclusions: A significant proportion of osteosarcoma tumors express IGF-R and ligands. Higher levels of expression were not correlated with metastatic lesions.

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Insulin-like growth factor-I is an autocrine regulator for the brain metastatic variant of a human non-small cell lung cell line

Cited by 9 publications

References 14 publications

Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells

Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells

An enhanced and sensitive autocrine stimulation by transforming growth factor-α is acquired in the brain metastatic variant of a human non-small-cell lung cancer cell line

Expression of insulin-like growth factor receptor, IGF-1, and IGF-2 in primary and metastatic osteosarcoma

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