Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells.

Clinton, Gail M.; Rougeot, Christian; Derancourt, Jean; Roger, Pascal; Defrenne, Annick; Godyna, S; Argraves, W. Scott; Rochefort, Henri

doi:10.1073/pnas.93.1.316

Cited by 74 publications

(64 citation statements)

References 25 publications

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“…Although coordinated expression of these two isoforms has been described , abnormal differential expression of the two isoforms in tumour tissues cannot be excluded. Since the two isoforms appear to have an opposite effect on tumour aggressiveness (Clinton et al, 1996;Qing et al, 1997;Roger et al, 1998;Twal et al, 2001;Du et al, 2002), the failure to discriminate the isoforms expressed in our series might have masked any impact on survival. The availability of isoform-specific reagents will enable analyses of potentially altered expression of the two isoforms.…”

Section: Discussionmentioning

confidence: 99%

Immunological and pathobiological roles of fibulin-1 in breast cancer

et al. 2003

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Fibulin-1 (Fbln-1) is an immunogenic breast cancerrelated glycoprotein identified by serological analysis of cDNA expression library (SEREX) strategy. Here, we show that dendritic cells from two breast cancer patients elicited a CD4 þ -mediated T-cell response to Fbln-1 presentation. In both patients, an antibody response to Fbln-1 was also found. By contrast, a Fbln-1-seronegative patient and a weakly seropositive patient demonstrated no such T-cell response. Analysis of human breast cancers for Fbln-1 RNA and protein expression revealed the presence of Fbln-1C and -1D variants. Fbln-1 was detected in the cytoplasm and at the cell surface of different human breast carcinoma cell lines. Immunohistochemical analysis of 528 archival primary breast carcinomas showed the expression of Fbln-1 in 35% of the cases. When the immunohistochemical findings were compared against pathobiological information associated with each specimen, an inverse relationship between Fbln-1 and cathepsin D expression was observed (P ¼ 0.04). Furthermore, even though long-term survival was similar between Fbln-1-positive and -negative cases, the survival of Fbln-1-positive cases improved when a lymphoid infiltrate was present at the tumour site. Taken together, our findings of an Fbln-1-specific immunity and the improved survival associated with Fbln-1 expression in the presence of lymphoid infiltration point to a role of Fbln-1 in tumour immunosurveillance.

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Section: Discussionmentioning

confidence: 99%

Immunological and pathobiological roles of fibulin-1 in breast cancer

et al. 2003

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“…Since there are four di erent alternatively spliced ®bulin-1 variants that may have distinct biological properties (Argraves et al, 1990;, we analysed the induction of ®bulin-1 variants and their relative expression in ovarian cancer cells. In this study, the induction of ®bulin-1 by estradiol ± previously described at the protein level (Galtier-Dereure et al, 1992;Clinton et al, 1996) ± is con®rmed at the mRNA level and is likely mediated through ERa. Moreover, we show that ®bulin-1C mRNA is more expressed than ®bulin-1D mRNA in ovarian cancer cells as compared to normal ovaries.…”

Section: Discussionmentioning

confidence: 99%

“…The ®bulin-1 protein is also present in the stroma of breast and ovarian tumors (Clinton et al, 1996;Roger et al, 1998). We have recently shown that ®bulin-1 protein expression is increased in human ovarian epithelial cancers as compared to normal and benign tumors and that epithelial ovarian cells expressed ®bulin-1 mRNA in vivo .…”

Section: Introductionmentioning

confidence: 93%

“…Expression of c-myc (Chien et al, 1994), IGFBP-5 (Krywicki et al, 1993), BRCA1 (Romagnolo et al, 1998) and cathepsin D (Galtier-Dereure et al, 1992) is increased by estradiol treatment of ovarian cancer cell lines. Our laboratory previously described a major secreted protein regulated by estradiol in ERpositive ovarian cancer cell lines (Galtier-Dereure et al, 1992) and identi®ed this protein as ®bulin-1 (Clinton et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Katsaros²,

et al. 2002

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Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of ®bulin-1 mRNA results in four di erent variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of ®bulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, ®bulin-1C and -1D are the predominant forms, whereas ®bulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coampli®cation of ®bulin-1C and -1D to study the relative expression of these ®bulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the ®bulin-1C:1D and ®bulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, ®bulin-1C mRNA was induced by estradiol in a dose-and time-dependent manner. Since others and we have previously shown an increased expression of ERa as compared to ERb in ovarian cancer cells, we investigated whether ERa or ERb is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and ®bulin-1, was infected with recombinant ERa or ERb encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERa-but not ERb-infected cells, suggesting that ®bulin-1C induction is mediated through ERa. In ovarian tumors, a trend towards a correlation between ®bulin-1C and ERa expression levels was noted. In conclusion, this study showed an increased ®bulin-1C: -1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This ®nding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERa promoted ovarian tumor progression.

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“…In keeping, we found that glycoprotein fibulin-1 (FBLN-1), a cysteine-rich, calcium-binding ECM and plasma molecule (Argraves et al, 1990), is aberrantly overtranscribed in epithelial tumor cell lines and breast surgical specimens, and that the protein is accumulated in the breast cancer-associated stroma, as detected immunohistochemically (Forti et al, 2002). Augmented expression of FBLN-1 has been also reported in human ovarian cancer cells stimulated with estrogens, and the resulting overexpression facilitated ovarian tumor cell invasion and progression (Clinton et al, 1996;Moll et al, 2002). FBLN-1 self-associates and binds to other ECM proteins, including fibronectin, laminin and nidogen, and to fibrinogen (Roark et al, 1995).…”

Section: Oncogenic Signals Of Ecm Componentsmentioning

confidence: 96%

New insights into the role of extracellular matrix during tumor onset and progression

Pupa

Ménard

Forti

et al. 2002

Journal Cellular Physiology

303

210

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Recently, a view of the tumor as a functional tissue interconnected with the microenvironment has recently been described. For many years, the stroma has been studied in the context of the malignant lesion, and only rarely has its role been considered before carcinogenic lesions appear. Recent studies have provided evidence that stromal cells and their products can cause the transformation of adjacent cells through transient signaling that leads to the disruption of homeostatic regulation, including control of tissue architecture, adhesion, cell death, and proliferation. It is now well established that tumor progression requires a continually evolving network of interactions between neoplastic cells and extracellular matrix. A relevant step of this process is the remodeling of microenvironment which surrounds tumors leading to the release of ECM-associated growth factors which can then stimulate tumor and/or endothelial cells. Finally, tumor cells reorganizing the extracellular matrix to facilitate communications and escape the homeostatic control exerted by the microenvironment modify response to cytotoxic treatments.

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Estrogens increase the expression of fibulin-1, an extracellular matrix protein secreted by human ovarian cancer cells.

Cited by 74 publications

References 25 publications

Immunological and pathobiological roles of fibulin-1 in breast cancer

Immunological and pathobiological roles of fibulin-1 in breast cancer

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

New insights into the role of extracellular matrix during tumor onset and progression

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