A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis

Nau, Gerard J.; Guilfoile, Patrick; Chupp, Geoffrey; Berman, Jeffrey S.; Kim, Sue J.; Kornfeld, Hardy; Young, Richard A.

doi:10.1073/pnas.94.12.6414

Cited by 183 publications

(161 citation statements)

References 46 publications

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“…Under normal physiological conditions, OPN plays an important role in the cells of the immune system, especially in macrophages (Nau et al, 1999;Chabas et al, 2001). It is involved in cell migration (Nau et al, 1999), remodeling of the extracellular matrix (Subha et al, 2001), and angiogenesis (Fumiyuki et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…It is involved in cell migration (Nau et al, 1999), remodeling of the extracellular matrix (Subha et al, 2001), and angiogenesis (Fumiyuki et al, 2002). These functions are also characteristics of cancer cell metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…We isolated the promoter of OPN and analysed the regulatory sequence for factors that interact with this sequence. Previous studies of the OPN promoter have been demonstrated on normal cells from the immune system (Nau et al, 1999;Chabas et al, 2001). However, it is not clear whether the tumor cells use the same mechanism during metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…It not only contributes to cellular immunity and macrophage homing, but also induces migration of immune cells and invasion to inflammatory sites in host-resistant systems (Nau et al, 1999;Chabas et al, 2001). It is believed that tumor cells require the same mechanism in the process of metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional regulation of human osteopontin promoter by C/EBPα and AML-1 in metastatic cancer cells

2004

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Osteopontin (OPN) is a secreted glycoprotein produced by osteoclasts, macrophages, T cells, hematopoietic cells, and vascular smooth muscle cells. It contributes to macrophage homing and cellular immunity. It also mediates neovascularization, inhibits apoptosis, and plays important roles in extracellular matrix remodeling and angiogenesis. These properties are also characteristics of metastatic cancer cells. Consequently, the OPN gene was found to be upregulated among various metastatic cancer cells. This suggests that OPN is involved in tumor metastasis. How the OPN gene is upregulated in metastatic cancer cells remains to be illustrated. Thus, we investigated the transcriptional activation of the OPN promoter in the human metastatic cancer cell line A2058. We cloned the OPN promoter, and serial deletion analysis of the OPN promoter showed that the region between -170 and -127 may act as an enhancer to control the OPN gene in metastatic tumor cells. This region was found to contain overlapped AML-1 and C/EBP binding site motifs. Gel-mobility-shift assays using the A2058 nuclear extract and AML-1a or C/EBPa (CCAAT/ enhancer binding protein alpha) recombinant protein indicated that these two transcription factors can bind to the overlapped AML-1 /C/EBP binding site motifs on the OPN regulatory sequence from -147 to -127. Surprisingly, the gel-shift experiments did not show supershift complex formation between AML-1 and C/EBPa. Functional analysis showed that the C/EBPa was more potent than the complex of AML-1 and its cofactor CBFb to upregulate the OPN promoter. In addition, AML-1 and C/EBPa did not exhibit transactivation additively or synergistically. Our results suggest that AML-1 and C/ EBPa play an important role in the upregulation of the OPN gene in metastatic tumor cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcriptional regulation of human osteopontin promoter by C/EBPα and AML-1 in metastatic cancer cells

2004

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“…In contrast, expression of OPN mRNA, another commonly used marker of initial osteoblast differentiation, was increased by BCG infection. In this connection, Nau et al (39,40) found that M. tuberculosis, but not E. coli, infection of macrophages causes a substantial increase in OPN gene expression and that OPN augments the protective host response against a mycobacterial infection.…”

Section: -1bb Induction In Osteoblasts and Osteoclastogenesismentioning

confidence: 99%

Infection-induced Up-regulation of the Costimulatory Molecule 4-1BB in Osteoblastic Cells and Its Inhibitory Effect on M-CSF/RANKL-induced in Vitro Osteoclastogenesis

Saito

Ohara

Hotokezaka

et al. 2004

Journal of Biological Chemistry

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Bacterial infection sometimes impairs bone metabolism. In this study, we infected the osteoblastic cell line MC3T3-E1 with Mycobacterium bovis bacillus CalmetteGué rin (BCG) and identified genes that were up-regulated in the BCG-infected cells by the suppression subtractive hybridization method. A gene encoding 4-1BB (CD137), a member of the tumor necrosis factor-␣ receptor family, was found to be one of the up-regulated genes. Up-regulation of 4-1BB was also observed by infection with Escherichia coli, Salmonella typhimurium, and Tuberculosis is an ancient disease but still ranks as one of the foremost killers of the 21st century. About one-third of the world's population is infected with Mycobacterium tuberculosis and more than two million people die annually from tuberculosis (1). Most tuberculosis cases are pulmonary, but the microorganism sometimes invades the central nervous system, the lymphatic system, and the musculoskeletal system, or is sometimes disseminated throughout the whole body. Mycobacterium infection in bones and joints presents ϳ10% of the extra-pulmonary cases (2). Vertebral osteomyelitis and osteitis also occur as a complication of vaccination with bacillus Calmette-Guérin (BCG) 1 or intravesical use of BCG (3, 4). Osteomyelitis and osteitis caused by M. tuberculosis or BCG infection sometimes lead to vertebral caries in some patients as a result of increased bone resorption.Bone is maintained by dynamic equilibrium between osteoblasts and osteoclasts in bone marrow cells. M. tuberculosis and BCG infection of bone alters this equilibrium, resulting in the loss of extracellular matrix and collapse of bone, especially vertebrae. Whether this bone resorption is attributable to direct effects of the bacteria on bone cells or infection-induced activation of inflammatory cells has not been clarified. However, a few studies have shown that mycobacterial antigens interfere with bone metabolism. Wax D, a mycobacterial cell wall peptidoglycan fragment-arabinogalactan-mycolic acid complex, induced reactive bone formation accompanied with osteomyelitis in Buffalo rats (5). Heat shock protein 10 of M. tuberculosis stimulates bone resorption in bone explanting cultures and induces osteoclast recruitment but inhibits proliferation of an osteoblast bone-forming cell line (6). The secreted protein MPB70 of BCG has significant homology with four repeat domains of osteoblast-specific factor 2/periostin (7). Epidemiological study suggests that MPB70-overproducing strains of BCG seem to be associated with an increased incidence of osteitis after BCG vaccination of neonates (7).Osteoblasts express various enzymatic markers such as alkaline phosphatase (ALP) and produce collagenous and noncol-

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Osteopontin as a Potential Diagnostic Biomarker for Ovarian Cancer

Kim

Skates

Uede

et al. 2002

JAMA

409

278

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Recent studies posit a role for non-coding RNAs in epithelial ovarian cancer (EOC). Combining small RNA sequencing from 179 human serum samples with a neural network analysis produced a miRNA algorithm for diagnosis of EOC (AUC 0.90; 95% CI: 0.81-0.99). The model significantly outperformed CA125 and functioned well regardless of patient age, histology, or stage. Among 454 patients with various diagnoses, the miRNA neural network had 100% specificity for ovarian cancer. After using 325 samples to adapt the neural network to qPCR measurements, the model was validated using 51 independent clinical samples, with a positive predictive value of 91.3% (95% CI: 73.3-97.6%) and negative predictive value of 78.6% (95% CI: 64.2-88.2%). Finally, biologic relevance was tested using in situ hybridization on 30 pre-metastatic lesions, showing intratumoral concentration of relevant miRNAs. These data suggest circulating miRNAs have potential to develop a non-invasive diagnostic test for ovarian cancer.

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A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis

Cited by 183 publications

References 46 publications

Transcriptional regulation of human osteopontin promoter by C/EBPα and AML-1 in metastatic cancer cells

Transcriptional regulation of human osteopontin promoter by C/EBPα and AML-1 in metastatic cancer cells

Infection-induced Up-regulation of the Costimulatory Molecule 4-1BB in Osteoblastic Cells and Its Inhibitory Effect on M-CSF/RANKL-induced in Vitro Osteoclastogenesis

Osteopontin as a Potential Diagnostic Biomarker for Ovarian Cancer

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