Human fibulin‐4: analysis of its biosynthetic processing and mRNA expression in normal and tumour tissues

Gallagher, William M.; Greene, Lisa M.; Ryan, Michael P.; Sierra, Véronique; Berger, Anne; Laurent‐Puig, Pierre; Conseiller, Emmanuel

doi:10.1016/s0014-5793(00)02389-9

Cited by 61 publications

(58 citation statements)

References 37 publications

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“…Moreover, high fibulin-4 expression was associated with low differentiation, advanced stage and positive lymph node status in the cervical carcinomas. Similar results have been reported in earlier studies on colon cancer; dysregulated expression of the fibulin-4 gene was shown to be associated with human colon tumorigenesis (33). However, contrasting results have also been reported for prostate cancer.…”

Section: Discussionsupporting

confidence: 89%

“…Fibulin-4 plays a role in many clinical conditions such as cutis laxa (30), aortic aneurysms (31), osteoarthritis (32) and cancer (22,33). In their study on colon tumors, Gallagher et al found that the fibulin-4 gene was localized on chromosome 11q13 (33); translocations, amplifications and other rearrangements in this region are associated with a variety of human cancers (34,35).…”

Section: Introductionmentioning

confidence: 99%

“…In their study on colon tumors, Gallagher et al found that the fibulin-4 gene was localized on chromosome 11q13 (33); translocations, amplifications and other rearrangements in this region are associated with a variety of human cancers (34,35). Reverse transcriptase (RT)-polymerase chain reaction (PCR) of RNA from paired human colon tumors and adjacent normal tissue showed that tumors had a 2-7 fold increase in the level of fibulin-4 mRNA expression (33). However, in prostate cancer (22), fibulin-4 was found to be significantly downregulated and weakly expressed in carcinoma cell lines compared to normal prostate epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma

et al. 2014

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Abstract. Fibulin-4, a member of the fibulin family of extracellular glycoproteins, is implicated in the progression of a number of types of cancer. However, the function of fibulin-4 in cervical cancer progression remains unexplored. Fibulin-4 mRNA and protein expression levels in normal cervical tissue, cervical intraepithelial neoplasia (CIN), cervical carcinoma, highly invasive subclones and low-invasive subclones were evaluated by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. Serum fibulin-4 levels in patients with CIN and cervical carcinoma were measured by enzyme-linked immunosorbent assay. To assess the angiogenic properties of fibulin-4, vascular endothelial growth factor (VEGF) expression and tumor microvessel density (MVD) were analyzed in the cervical carcinoma cases by immunohistochemistry. Fibulin-4 expression was upregulated in the cervical carcinoma cases, and was positively correlated with MVD and VEGF expression. Fibulin-4 overexpression and high serum levels were significantly associated with advanced stage, low differentiation, lymph node metastasis, and poor prognosis in patients with cervical cancer. Fibulin-4 expression was also found to be overexpressed in highly invasive subclones when compared with the low-invasive subclones. Fibulin-4 is a newly identified glycoprotein that is overexpressed in cervical carcinoma. Fibulin-4 promotes angiogenesis and is associated with poor prognostic clinicopathologic features. This study demonstrated that fibulin-4 may serve as a new prognostic factor and as a potential therapeutic target for patients with cervical carcinoma.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma

et al. 2014

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“…Likewise, Fibulin-4 expression promotes the growth of normal and abnormal cells through p53-independent and -dependent mechanisms, respectively. With respect to the latter, signal sequence polymorphisms in the Fibulin-4 gene prevent its secretion from human colon cancer cells (28). This intracellular variant of Fibulin-4 then interacts with and inhibits the activity of p53, leading to enhanced proliferation of tumor cells (22).…”

Section: Discussionmentioning

confidence: 99%

Context-specific Effects of Fibulin-5 (DANCE/EVEC) on Cell Proliferation, Motility, and Invasion

Schiemann¹,

Blobe²,

Kalume³

et al. 2002

Journal of Biological Chemistry

144

100

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The Fibulin gene family comprises five distinct genes that encode more than eight protein products via alternative splicing. Fibulins are widely expressed secretory proteins found in the blood and in the basement membranes and stroma of most tissues, where they self-associate (e.g. Fibulins 1 and 2) (1, 2) and/or interact with a variety of extracellular matrix components, including fibronectin, laminin, nidogen, aggrecan, versican, endostatin, and elastin (3-5). Thus, Fibulins likely participate in the assembly and stabilization of extracellular matrix structures; they also have been implicated in regulating organogenesis, vasculogenesis, fibrogenesis, and tumorigenesis (6 -8). Although the molecular mechanisms underlying the various biological activities of Fibulins remain to be elucidated, recent work suggests that Fibulins may interact directly with cell surface receptors, raising the possibility that these secretory proteins also function in mediating cell-cell and cell-matrix communication.The newest member of the Fibulin family is Fibulin-5 (FBLN-5; also known as EVEC (9) or DANCE (10)), 1 a 448-amino acid glycoprotein with interesting structural features; it contains an integrin-binding RGD motif, six calcium-binding epidermal growth factor-like repeats, a Pro-rich insert in the first calcium-binding epidermal growth factor-like repeat, and a globular C-terminal domain (9, 10). Functionally, FBLN-5 binds ␣ v ␤ 3 , ␣ v ␤ 5 , and ␣ 9 ␤ 1 integrins (4) and mediates endothelial cell adhesion via its RGD motif (10). In response to mechanical injury, FBLN-5 expression is induced dramatically in vascular endothelial and smooth muscle cells (9, 10), suggesting that FBLN-5 regulates vasculogenesis and endothelial cell function. Inactivation of the FBLN-5 gene in mice produces profound elastinopathy in the skin, lung, and vasculature (4, 5), demonstrating its importance in scaffolding cells to elastic fibers.Despite these recent advances, many questions regarding the role of FBLN-5 in mammalian biology remain to be answered, particularly (i) what are the signaling systems/molecules that regulate (ii) what are the effects of FBLN-5 on cell proliferation, migration, and invasion, and (iii) what are the signaling systems/molecules stimulated by FBLN-5. Through the use of expression proteomics, we show here that FBLN-5 is a novel TGF-␤-inducible protein that

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“…Whereas fibulin-1 was shown to mediate chemoresistance in breast cancer and furthermore seems to play a role in tumor immunosurveillance (7,8), loss of fibulin-2 results in breast cancer progression (9). Other reports imply a role of the fibulins in colon cancer tumorigenesis and breast cancer epithelialmesenchymal transition (10,11).…”

Section: Introductionmentioning

confidence: 99%

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

Seeliger¹,

Čamaj²,

Ischenko³

et al. 2009

Molecular Cancer Research

100

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The progression of pancreatic cancer is dependent on local tumor growth, angiogenesis, and metastasis. EFEMP1, a recently discovered member of the fibulin family, was characterized with regard to these key elements of pancreatic cancer progression. Differential gene expression was assessed by mRNA microarray hybridization in FG human pancreatic adenocarcinoma cells and L3.6pl cells, a highly metastatic variant of FG. In vivo orthotopic tumor growth of EFEMP1-transfected FG cells was examined in nude mice. To assess the angiogenic properties of EFEMP1, vascular endothelial growth factor (VEGF) production of tumor cells, endothelial cell proliferation and migration, and tumor microvessel density were analyzed in response to EFEMP1. Further, tumor cell apoptosis, cell cycle progression, and resistance to cytotoxic agents were quantitated by propidium iodide staining and flow cytometry. In microarray hybridization, EFEMP1 was shown to be significantly up-regulated in L3.6pl cells compared with FG cells. Concordantly, EFEMP1 transfection of FG cells stimulated orthotopic and metastatic tumor growth in vivo. EFEMP1 expression resulted in a stimulation of VEGF production by tumor cells and an increased number of CD31-positive microvessels. Endothelial cell proliferation and migration were not altered by EFEMP1, indicating an indirect angiogenic effect. Further, EFEMP1 expression decreased apoptosis and promoted cell cycle progression in response to serum starvation or exposure to gemcitabine, 5-fluorouracil, and irinotecan. EFEMP1 has protumorigenic effects on pancreatic cancer in vivo and in vitro mediated by VEGF-driven angiogenesis and antiapoptotic mechanisms. Hence, EFEMP1 is a promising candidate for assessing prognosis and individualizing therapy in a clinical tumor setting. (Mol Cancer Res 2009;7(2):189-98)

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Human fibulin‐4: analysis of its biosynthetic processing and mRNA expression in normal and tumour tissues

Cited by 61 publications

References 37 publications

Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma

Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma

Context-specific Effects of Fibulin-5 (DANCE/EVEC) on Cell Proliferation, Motility, and Invasion

EFEMP1 Expression Promotes In vivo Tumor Growth in Human Pancreatic Adenocarcinoma

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