Fibulin-3 Is Uniquely Upregulated in Malignant Gliomas and Promotes Tumor Cell Motility and Invasion

Hu, Bin; Rajamani, Keerthi Thirtamara; Sim, Hosung; Viapiano, Mariano S.

doi:10.1158/1541-7786.mcr-09-0207

Cited by 122 publications

(166 citation statements)

References 59 publications

Supporting

Mentioning

164

Contrasting

Order By: Relevance

“…Fibulin-3 has been found to be downregulated in several types of solid tumors (14) but surprisingly, is the most upregulated member of the fibulin family in malignant gliomas (15). Fibulin-3 is also upregulated in aggressive pancreatic adenocarcinoma, resulting in enhanced in vivo orthotopic and metastatic tumor growth (16).…”

Section: Discussionmentioning

confidence: 99%

Role of fibulin-3 in lung cancer: In vivo and in vitro analyses

Yang

Sun

et al. 2013

Oncology Reports

View full text Add to dashboard Cite

Abstract. Lung cancer was the most commonly diagnosed cancer in 2008 worldwide. The level of fibulin-3 expression was found to be decreased in many cancer types due to aberrant promoter methylation and is correlated with poor survival of patients. However, the role of fibulin-3 and which form of fibulin-3 is expressed in lung cancer cells remain unclear. Therefore, pathologic and functional studies were carried out to determine the role of fibulin-3 in suppressing lung cancer both in vivo and in vitro. In the present study, we found that the levels of fibulin-3 mRNA and protein were lower in cancer tissues than in normal tissues. Downregulation of fibulin-3 mRNA in tumor tissues was associated with an increase in fibulin-3 promoter methylation. Circulating fibulin-3 was significantly associated with tumor progression, survival rate of lung cancer patients, and the number of circulating tumor cells (CTCs). To examine the effects of exogenous expression of fibulin-3 in vitro, lung cancer A549 cells were transfected with the pEGFP-C1-fibulin-3 expression vector. Relative to the untreated cells, fibulin-3-expressing cells exhibited lower proliferation and mobility as determined by MTT and Transwell assays, respectively. To conclude, our results suggest that fibulin-3 negatively modulates the invasiveness of lung cancer cells via regulation of p38-MAPK and MMP-2/9. IntroductionLung cancer was the most commonly diagnosed cancer as well as the leading cause of cancer-related mortality in males in 2008 worldwide (1). Similar to other cancers, lung cancer is thought to be caused by the deregulation of normal gene expression (2).Fibulins are widely distributed and are localized at basal membranes mediating cell-to-cell and cell-to-matrix communication. They are characterized by repeated epidermal growth factor (EGF)-like domains and a unique C-terminal structure (3,4). The relationship of the fibulin gene family members and many types of cancer has been reported (5-7). The fibulin-3 gene, also known as EFEMP1 (epidermal growth factorcontaining fibulin-like extracellular matrix protein 1) located at chromosome 2p16, is one of the 7 members of the fibulin gene family of extracellular glycoproteins (8). The level of fibulin-3 expression was found to be decreased in many cancer types due to aberrant promoter methylation and is correlated with poor survival of patients with breast cancer (9) lung cancer (10) and hepatocellular carcinoma (11). Lecka-Czernik et al (12) predicted that this protein has 2 possible isoforms, a ̔longʼ form of 53 to 55 kDa, with an NH2-terminal Ca 2+ -binding epidermal growth factor-like repeat, and a ̔shortʼ form of 40 to 43 kDa without this domain. However, which form of fibulin-3 is expressed in lung cancer cells remains unclear.Pathologic and functional studies were carried out to determine the role of fibulin-3 in suppressing lung cancer both in vivo and in vitro. Further elucidation of the functions of fibulin-3 may lead to a better understanding of the pathogenesis of lung cancer. Fibulin-3 is ...

show abstract

Section: Discussionmentioning

confidence: 99%

Role of fibulin-3 in lung cancer: In vivo and in vitro analyses

Yang

Sun

et al. 2013

Oncology Reports

View full text Add to dashboard Cite

show abstract

“…MMP-9 and MMP-2 are important ECM-degrading enzymes that are reported to be involved in cancer cell invasion and metastasis (20). On the basis of these observations and the foregoing data, we examined the effect of shikonin on the expression of both MMP-2 and MMP-9 in MDA-MB-231 cells; we also investigated PMA-induced MMP-9 expression in MCF-7 cells.…”

Section: Shikonin Inhibits Mmp-9 Expression and Proteolytic Activitymentioning

confidence: 99%

Shikonin blocks migration and invasion of human breast cancer cells through inhibition of matrix metalloproteinase-9 activation

et al. 2014

View full text Add to dashboard Cite

Abstract. Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, has been reported to promote tumor cell death. However, there are few reports concerning its effect on metastasis-related cell invasion and migration behavior. In the present study, we investigated the effect of shikonin on human breast cancer invasion and migration. We found that shikonin inhibited phorbol 12-myristate 13-acetate (PMA)-induced cell migration and invasion in MCF-7 breast cancer cells, which was correlated with modulation of matrix metalloproteinase-9 (MMP-9) through suppression of both expression and proteolytic and promoter activity. We also found that shikonin inhibited both MMP-9 expression and promoter activity in MDA-MB-231 cells with high metastatic potential. These results indicated that shikonin induces the suppression of migration and invasion through modulation of MMP-9 in human breast cancer cells. Therefore, shikonin may be a potential anticancer drug for human breast cancer therapy. IntroductionBreast cancer ranks among the most common malignant tumors afflicting women worldwide (1). Cancer metastasis is the leading cause of mortality in patients with breast cancer; breast cancer survival rates fall from 90% for localized to 20% for metastatic disease. Therefore, controlling metastasis and invasion represents an important therapeutic strategy (2). Metastasis requires that invasive cells detach from localized tumors by degrading the extracellular matrix using proteases, including matrix metalloproteinases (MMPs); survive in the circulation as circulating tumor cells (CTCs); and colonize distant locations. Thus, understanding the molecular mechanisms underlying each of these steps is essential for targeting metastatic cells at an early stage and improving patient survival (3).MMPs are a family of extracellular matrix (ECM)-degrading enzymes comprising 24 members. Based on their substrates, MMPs are divided into four subclasses: collagenase, gelatinase, stromelysin and membrane-associated (4). As a main ECM-degrading enzyme family, MMPs have essential roles in physiologic processes such as tissue development, remodeling and wound healing (5). However, they are also involved in certain tissue destructive diseases, such as atherosclerosis, inflammation, rheumatoid arthritis, and tumor invasion, metastasis and neoangiogenesis (6). Recent studies have shown that MMPs are important elements of the tumor microenvironment, regulating tumor progression, metastatic niche formation and inflammation in cancer (7). Among human MMPs, MMP-2 (gelatinase-A) and MMP-9 (gelatinase-B) are key enzymes in the degradation of type IV collagen, which is an important component of the ECM. MMP-2 and MMP-9 are the MMP members primarily associated with tumor migration, invasion and metastasis of various types of cancers (8). It has been shown that enhanced expression of MMP-9 is associated with the progression and invasion of tumors, whereas MMP-2 is usually expressed constitutively (9,10). Thus, researchers have focu...

show abstract

“…CADPE inhibits MMP-9 expression and activity MMP-9 and MMP-2 are important ECM-degrading enzymes. It has been reported that both enzymes were involved in cancer cell invasion and metastasis (14,29). The fact that CADPE inhibited cancer cell invasion prompted us to examine the effect of CADPE on MMPs activity using gelatin zymography.…”

Section: Effects Of Cadpe On the Viability And Invasion Of Gastric Camentioning

confidence: 99%

CADPE Inhibits PMA-Stimulated Gastric Carcinoma Cell Invasion and Matrix Metalloproteinase-9 Expression by FAK/MEK/ERK–Mediated AP-1 Activation

Han

Pan

et al. 2010

Molecular Cancer Research

View full text Add to dashboard Cite

Metastasis is one of the main causes of death for patients with malignant tumors. Aberrant expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of various cancer cells. Here, we found that caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) could inhibit the migration and invasion of human gastric carcinoma cells in Transwell migration assays. To understand the underlying mechanism, we showed that CADPE significantly inhibited phorbol 12-myristate 13-acetate (PMA)-induced increases in MMP-9 expression and activity in a dose-dependent manner. The inhibitory effect of CADPE on MMP-9 expression correlated well with the suppression of MMP-9 promoter activity and the reduction of MMP-9 mRNA. Reporter gene assay and electrophoretic mobility shift assay showed that CADPE inhibited MMP-9 expression by suppressing the activation of the nuclear transcription factor activator protein-1 (AP-1) and c-Fos, but not NF-κB. Moreover, CADPE inhibited PMA-induced phosphorylation of protein kinases involved in AP-1 activation, such as focal adhesion kinase (FAK), mitogen-activated protein kinase/ extracellular signal-regulated kinase (ERK) kinase (MEK), and ERK1/2, whereas CADPE had little effect on the phosphorylation of p38 and c-jun NH 2 -terminal kinase. Taken together, our findings indicate that CADPE could be a unique antitumor agent that specifically inhibits MMP-9 activity by targeting the activation of FAK/ MEK/ERK protein kinases and AP-1 transcription factor.

show abstract

Fibulin-3 Is Uniquely Upregulated in Malignant Gliomas and Promotes Tumor Cell Motility and Invasion

Cited by 122 publications

References 59 publications

Role of fibulin-3 in lung cancer: In vivo and in vitro analyses

Role of fibulin-3 in lung cancer: In vivo and in vitro analyses

Shikonin blocks migration and invasion of human breast cancer cells through inhibition of matrix metalloproteinase-9 activation

CADPE Inhibits PMA-Stimulated Gastric Carcinoma Cell Invasion and Matrix Metalloproteinase-9 Expression by FAK/MEK/ERK–Mediated AP-1 Activation

Contact Info

Product

Resources

About