Acidic fibroblast growth factor mRNA is expressed by cardiac myocytes in culture and the protein is localized to the extracellular matrix.

Weiner, Henry; Swain, Judith L.

doi:10.1073/pnas.86.8.2683

Cited by 116 publications

(41 citation statements)

References 30 publications

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“…RNA bands of ϳ6.0, 4.2, and 3.1 kb were present, as has been described in cardiac myocytes. 19 As can be seen in Figure 8A, IL-8 induced increased levels of FGF2 mRNA as early as 6 hours after treatment. By densitometry, after normalization for variation in mRNA loading using control glyceraldehyde-3Ј-phosphate dehydrogenase hybridization a sevenfold increase in FGF2 mRNA levels was present at 6 hours, which decreased slightly by 24 hours.…”

Section: Il-8 Increases Fgf2 Mrna In Prostatic Stromal Cellsmentioning

confidence: 64%

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Giri

Ittmann

2001

The American Journal of Pathology

119

103

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Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in which there is benign overgrowth of the prostatic transition zone, leading to obstruction of urine outflow. Fibroblast growth factor (FGF) 2, a potent growth factor for prostatic stromal and epithelial cells, is increased twofold in BPH and its concentration is correlated with stromal proliferation in this condition. Immunohistochemistry of normal and hyperplastic prostate revealed that FGF2-expressing stromal cells were present in higher numbers near the epithelial acini, implying that epithelial cells may express a factor that induces FGF2 expression by stromal cells. Benign prostatic hyperplasia (BPH) is an extremely common condition of older men, such that by 70 years of age the majority of men exhibit clinical symptoms of this disease. 1 The benign growth of the prostatic transition zone that is characteristic of BPH leads to obstruction of urine outflow and in this manner causes considerable morbidity. Thus BPH is of considerable medical importance and yet its pathogenesis is still obscure.Prostate growth is controlled by a variety of polypeptide growth factors, including members of the fibroblast growth factor (FGF) gene family. 2 FGF2, FGF7, and FGF9 are all present in high concentrations in normal human prostate. 3-6 FGF2 is a potent growth factor for prostatic stromal cells. 4,6,7 In addition it can stimulate proliferation of primary prostatic epithelial cells in culture. 5,6 Thus FGF2 can act as both a paracrine growth factor for prostatic epithelial cells and as an autocrine growth factor for prostatic stromal cells.The concentration of both FGF7 4 and FGF2 3,4 are significantly increased in hyperplastic prostate in comparison to normal peripheral and transition zone tissue. FGF2 is a potent mitogen for prostatic stromal cells and quantitative analysis of cellular proliferation by Ki67 immunohistochemistry of frozen sections of the tissue taken before protein extraction revealed a correlation between increased FGF2 tissue concentration and increased proliferation of stromal cells in BPH tissue, 4 consistent with a key role for this growth factor in driving the abnormal stromal proliferation in BPH.Given that FGF2 protein is increased in BPH and that this overexpression has functional consequences for the proliferation of prostatic stromal cells, we sought to determine what factors control FGF2 expression in the human prostate. We report here that interleukin (IL)-8 is produced by prostatic epithelial cells and can act as a paracrine inducer of FGF2 production by prostatic stromal cells in vitro. In addition, we have found that IL-8 is present in substantial quantities in human prostate in vivo and that IL-8 concentration is elevated in BPH tissue. Thus stromal proliferation in BPH is controlled, at least in part, by IL-8 secreted by prostatic epithelial cells. This may ultimately lead to increased tissue mass in the prostatic transition zone, which is critical in the pathogenesis of BPH. Materials and Methods Tissue Acq...

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Section: Il-8 Increases Fgf2 Mrna In Prostatic Stromal Cellsmentioning

confidence: 64%

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Giri

Ittmann

2001

The American Journal of Pathology

119

103

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“…FGF1 has been localized extracellularly in vivo in the developing heart (Engelmann et al, 1993), tooth (Cam et al, 1992), lungs, digestive system, CNS and eye (Fu et al, 1991) where it is thought to act both as a paracrine growth factor as well as stimulating capillary and neural invasion. Weiner and Swain (1989) have shown that neonatal cardiac myocytes deposit FGF1 into their extracellular matrix and FGFR1 transcipts have been localized on developing cardiomyocytes (Engelman et al, 1993). Thus, tumorogenesis may mimic development in its mechanism of FGF1 action.…”

Section: Discussionmentioning

confidence: 99%

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue

Coope

Browne²,

Yiangou³

et al. 1997

Br J Cancer

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Summary Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4, were localized in cryostat sections of normal, benign and malignant human breast tissue by immunohistochemistry. Without pretreatment, FGF1 staining was mainly seen in normal epithelial cells. However, polymerase chain reaction (PCR) analysis and immunoblotting of isolated normal epithelial and myoepithelial cells showed FGF1 mRNA and protein to be present in both cell types. Following incubation of frozen sections at 370C in phosphate-buffered saline, FGF1 staining was also revealed in myoepithelial cells and basement membrane adjacent to carcinoma cells. Treatment with protease inhibitors demonstrated that this effect was due to the activity of an endogenous protease. In contrast, FGF1 staining was found to be associated with the stroma adjacent to malignant cells only in the presence of protease inhibitors. FGFR1 and FGFR4 immunostaining was localized to both normal and malignant epithelial cells and to a lesser extent to myoepithelial cells. There was no difference in the staining intensity for the FGF receptors between normal and cancer samples. The change in location of FGF1 between normal and malignant tissues and the sensitivity of stored FGF1 to the action of endogenous proteases raises the possibility of both autocrine and paracrine roles for FGF1 in the normal and malignant human breast.Keywords: breast cancer; fibroblast growth factor 1; protease; immunohistochemistry Fibroblast growth factor 1 (FGF1) belongs to a family of multifunctional polypeptides that are involved in a wide array of biological processes, which include cellular proliferation and differentiation, angiogenesis, chemotaxis, embryonal development and tissue repair (Basilico and Moscatelli, 1992). To date, the FGFs consist of a family of nine homologous polypeptide growth factors that include FGF1 (acidic FGF), FGF2 (basic FGF), FGF3 (int-2), FGF4 (hst-l/Kaposi FGF), FGF5, FGF6 (hst-2), FGF7 (keratinocyte growth factor), FGF8 (androgen-induced growth factor) and FGF9 (glial-activating factor) (Basilico and Moscatelli, 1992;Tanaka et al, 1992;Miyamoto et al, 1993). These proteins share 35-50% overall homology of their amino acid sequences (Basilico and Moscatelli, 1992;Givol and Yayon, 1992).Unlike other members of the family, FGF1, FGF2 and FGF9 are synthesized without a signal peptide sequence and thus may remain sequestered in the cell (Basilico and Moscatelli, 1992;Cao and Pettersson, 1993). However, release of FGF may occur through leakage from damaged cells or from viable cells via a novel mechanism (Mignatti et al, 1992;Cao and Pettersson, 1993). Yeoman (1993) has postulated that proteoglycan-bound FGF may be released from the cell surface or extracellular matrix by the action of proteases, and Briozzo et al (1991) have shown that Received 10 June 1996 Revised 26 November 1996 Accepted 3 December 1996 Correspondence to: J Gomm MCF7 breast cancer cells secrete cathepsin D, which is able to digest the extracellular matrix and releas...

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“…Both bFGF and aFGF can be detected in freshly isolated adult rat ventricular myocytes by immunohistochemistry, by Western analysis, and by immunoassay of mitogenic activity detected in myocyte cell lysates processed by heparin-Sepharose affinity chromatography (19)(20)(21)(22)59). In the intact heart, we have documented increased release by ELISA of both bFGF and aFGF in the perfusate of adult rat hearts retrogradely perfused for 5 min ex vivo in a Langendorff preparation with a physiologic saline solution containing 10 Ϫ7 M isoproterenol (60).…”

Section: Discussionmentioning

confidence: 99%

“…Both basic fibroblast growth factor (bFGF; FGF-2) and acidic fibroblast growth factor (aFGF; FGF-1) have been identified in terminally differentiated, postmitotic adult cardiac muscle cells, with subcellular localization to the cytoplasm, nucleus, and gap junctions at intercalated disks (18)(19)(20)(21)(22). FGFs released from these cells could act in an autocrine manner or on neighboring myocytes or other cell types in ventricular muscle.…”

Section: Introductionmentioning

confidence: 99%

Role of transiently altered sarcolemmal membrane permeability and basic fibroblast growth factor release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro.

Kaye¹,

Pimental²,

Prasad³

et al. 1996

J. Clin. Invest.

134

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One of the trophic factors that has been implicated in initiating or facilitating growth in response to increased mechanical stress in several tissues and cell types is basic fibroblast growth factor (bFGF; FGF-2). Although mammalian cardiac muscle cells express bFGF, it is not known whether it plays a role in mediating cardiac adaptation to increased load, nor how release of the cytosolic 18-kD isoform of bFGF would be regulated in response to increased mechanical stress. To test the hypothesis that increased mechanical activity induces transient alterations in sarcolemmal permeability that allow cytosolic bFGF to be released and subsequently to act as an autocrine and paracrine growth stimulus, we examined primary isolates of adult rat ventricular myocytes maintained in serum-free, defined medium that were continually paced at 3 Hz for up to 5 d. Paced myocytes, but not nonpaced control cells, exhibited a "hypertrophic" response, which was characterized by increases in the rate of phenylalanine incorporation, total cellular protein content, and cell size. These changes could be mimicked in control cells by exogenous recombinant bFGF and could be blocked in continually paced cells by a specific neutralizing anti-bFGF antibody. In addition, medium conditioned by continually paced myocytes contained significantly more bFGF measured by ELISA and more mitogenic activity for 3T3 cells, activity that could be reduced by a neutralizing anti-bFGF antibody. The hypothesis that transient membrane disruptions sufficient to allow release of cytosolic bFGF occur in paced myocytes was examined by monitoring the rate of uptake into myocytes from the medium of 10-kD dextran linked to fluorescein. Paced myocytes exhibited a significantly higher rate of fluoresceinlabeled dextran uptake. These data are consistent with the hypothesis that nonlethal, transient alterations in sarcolemmal membrane permeability with release of cytosolic bFGF is one mechanism by which increased mechanical activity could lead to a hypertrophic response in cardiac myocytes.( J. Clin. Invest. 1996. 97:281-291.)

show abstract

Acidic fibroblast growth factor mRNA is expressed by cardiac myocytes in culture and the protein is localized to the extracellular matrix.

Cited by 116 publications

References 30 publications

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue

Role of transiently altered sarcolemmal membrane permeability and basic fibroblast growth factor release in the hypertrophic response of adult rat ventricular myocytes to increased mechanical activity in vitro.

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