Enhancement of Tumor Necrosis Factor-α-Induced Growth Inhibition by Insulin-Like Growth Factor-Binding Protein-5 (IGFBP-5), But Not IGFBP-3 in Human Breast Cancer Cells

Butt, Alison J.; Dickson, Kristie A.; Jambazov, Stan; Baxter, Robert C.

doi:10.1210/en.2004-1408

Cited by 51 publications

(41 citation statements)

References 39 publications

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“…As mentioned earlier, IGFBP5 affects cell survival and apoptosis in a variety of cells, and the response to IGFBP5 depends on cell types. IGFBP5 induces apoptosis in mammary epithelial cells (Tonner et al 2002), breast cancer cells (Butt et al 2005), and osteosarcoma cells (Su et al 2011) but prevents apoptosis in neuroblastoma cells (Tanno et al 2006), C2 myoblasts (Cobb et al 2004), and human stellate cells (Sokolovic et al 2010). Although high glucose presently did not increase IGFBP5 protein levels in cardiomyocytes, the IGFBP5 released from cardiac fibroblasts may promote the apoptosis of cardiac myocytes.…”

Section: Discussionmentioning

confidence: 93%

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Song¹,

Kim²,

Kim³

et al. 2013

Journal of Molecular Endocrinology

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This study examined whether IGF-binding protein 5 (IGFBP5) is involved in the high glucoseinduced deteriorating effects in cardiac cells. Cardiac fibroblasts and cardiomyocytes were isolated from the hearts of 1-to 3-day-old Sprague Dawley rats. Treatment of fibroblasts with 25 mM glucose increased the number of cells and the mRNA levels of collagen III, matrix metalloproteinase 2 (MMP2), and MMP9. High glucose increased ERK1/2 activity, and the ERK1/2 inhibitor PD98059 suppressed high glucose-mediated fibroblast proliferation and increased collagen III mRNA levels. Whereas high glucose increased both mRNA and protein levels of IGFBP5 in fibroblasts, high glucose did not affect IGFBP5 protein levels in cardiomyocytes. The high glucose-induced increase in IGFBP5 protein levels was inhibited by PD98059 in fibroblasts. While recombinant IGFBP5 increased ERK phosphorylation, cell proliferation, and the mRNA levels of collagen III, MMP2, and MMP9 in fibroblasts, IGFBP5 increased c-Jun N-terminal kinase phosphorylation and induced apoptosis in cardiomyocytes. The knockdown of IGFBP5 inhibited high glucose-induced cell proliferation and collagen III mRNA levels in fibroblasts. Although high glucose increased IGF1 levels, IGF1 did not increase IGFBP5 levels in fibroblasts. The hearts of Otsuka Long-Evans Tokushima Fatty rats and the cardiac fibroblasts of streptozotocin-induced diabetic rats showed increased IGFBP5 expression. These results suggest that IGFBP5 mediates high glucose-induced profibrotic effects in cardiac fibroblasts.

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Section: Discussionmentioning

confidence: 93%

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Song¹,

Kim²,

Kim³

et al. 2013

Journal of Molecular Endocrinology

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“…We chose to focus on members of the TNF death-receptor family including TNFa and Fas, which induce apoptosis through pathways involving ligandmediated receptor activation. TNFa and CH11 (which trimerizes the Fas receptor) have been shown to promote apoptosis in tumour cells (Toillon et al 2002, Butt et al 2005. As seen in Fig.…”

Section: Discussionmentioning

confidence: 95%

Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-α, CH11 and CYC202

Mody

Dharker²,

Bloomston³

et al. 2007

Endocr Relat Cancer

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Peroxisome proliferator-activated receptor-g (PPARg) is a member of the nuclear hormone superfamily and has multiple endogenous and pharmacological ligands, including 15-deoxy-D 12,14 -prostaglandin J 2 and two thiazolidinediones (TZD), rosiglitazone and pioglitazone, which are used clinically to treat type-2 diabetes mellitus. PPARg agonists regulate development, cellular growth and metabolism in various tissues and have been documented to decrease cellular proliferation and to induce apoptosis of various tumour phenotypes, including breast cancer. However, the full spectrum of anti-tumour effects occurs only at suprapharmacological doses. In this study, we investigated the mechanism of rosiglitazone-induced anti-tumour effects of MDA-MB-231 human breast cancer cells, and used that information to predict rosiglitazone-induced sensitization of breast cancer cells to the effects of other compounds. We first confirmed that 100 mM rosiglitazone, but not lower doses, decreases MDA-MB-231 cell viability in vitro. We then used microarray gene expression analysis to determine early rosiglitazone-induced gene expression changes after 4-h exposure, which included 1298 genes that we grouped into functional categories. We selectively confirmed rosiglitazonemediated effects on expression of key regulators of breast cancer proliferation and apoptosis, including p53, p21 and Bax. Finally, we used this information to predict that rosiglitazone would sensitize MDA-MB-231 cells to the anti-tumour effects of CH11, which trimerizes Fas, as well as tumour necrosis factor-a. Moreover, we used the confirmed array data to predict cooperative activity of rosiglitazone and R-roscovitine (CYC202), an inhibitor of multiple cyclin-dependent kinases. We conclude that microarray analysis can determine early TZD-modulated changes in gene expression that help to predict effective in vitro drug combinations.

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“…In fact, there are many cases where the same IGFBP has been shown to have both stimulatory, as well as inhibitory effects on tumorigenesis, depending on the tumor type (Mukherjee and Rotwein, 2007). For example, IGFBP5 has been shown to induce caspase expression and promote apoptosis in breast cancer (Butt et al, 2003;Butt et al, 2005). In contrast, IGFBP5 is believed to facilitate prostate …”

Section: Discussionmentioning

confidence: 99%

“…IGFBP5 has been shown to traffic into the nucleus (Schedlich et al, 2000) and interact with transcription factors such as four-and-a-half LIM protein in U2 human OS cells, which can have downstream effects on tumor growth and metastasis (Amaar et al, 2002). In fact, nuclear localization of IGFBP5 has been associated with apoptosis in breast cancer (Butt et al, 2003;Butt et al, 2005) and inhibition of cell proliferation in murine OS/50-K8 OS cells (Schneider et al, 2001).…”

Section: Igfbp5 In Osteosarcomamentioning

confidence: 99%

Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

et al. 2011

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Osteosarcoma (OS) is the most common primary malignancy of bone. There is a critical need to identify the events that lead to the poorly understood mechanism of OS development and metastasis. The goal of this investigation is to identify and characterize a novel marker of OS progression. We have established and characterized a highly metastatic OS subline that is derived from the less metastatic human MG63 line through serial passages in nude mice via intratibial injections. Microarray analysis of the parental MG63, the highly metastatic MG63.2 subline, as well as the corresponding primary tumors and pulmonary metastases revealed insulin-like growth factor binding protein 5 (IGFBP5) to be one of the significantly downregulated genes in the metastatic subline. Confirmatory quantitative RT-PCR on 20 genes of interest demonstrated IGFBP5 to be the most differentially expressed and was therefore chosen to be one of the genes for further investigation. Adenoviral mediated overexpression and knockdown of IGFBP5 in the MG63 and MG63.2 cell lines, as well as other OS lines (143B and MNNG/HOS) that are independent of our MG63 lines, were employed to examine the role of IGFBP5. We found that overexpression of IGFBP5 inhibited in vitro cell proliferation, migration and invasion of OS cells. Additionally, IGFBP5 overexpression promoted apoptosis and cell cycle arrest in the G1 phase. In an orthotopic xenograft animal model, overexpression of IGFBP5 inhibited OS tumor growth and pulmonary metastases. Conversely, siRNA-mediated knockdown of IGFBP5 promoted OS tumor growth and pulmonary metastases in vivo. Immunohistochemical staining of patient-matched primary and metastatic OS samples demonstrated decreased IGFBP5 expression in the metastases. These results suggest 1) a role for IGFBP5 as a novel marker that has an important role in the pathogenesis of OS, and 2) that the loss of IGFBP5 function may contribute to more metastatic phenotypes in OS.

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Enhancement of Tumor Necrosis Factor-α-Induced Growth Inhibition by Insulin-Like Growth Factor-Binding Protein-5 (IGFBP-5), But Not IGFBP-3 in Human Breast Cancer Cells

Cited by 51 publications

References 39 publications

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

IGFBP5 mediates high glucose-induced cardiac fibroblast activation

Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-α, CH11 and CYC202

Insulin-like growth factor binding protein 5 suppresses tumor growth and metastasis of human osteosarcoma

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