Plasminogen activator inhibitor 2 in menstrual endometrium and in primary cultures of endometrial cells

Nordengren, Johanna; Casslén, Bertil; Lecander, Ingegerd

doi:10.1016/s0268-9499(96)80010-5

Cited by 6 publications

(7 citation statements)

References 29 publications

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“…The presence of PAI-2 in the normal endometrium is restricted to the menstrual period and seems to be related at least in part, to the appearance of macrophages. 43 The histologic localization of PAI-2 in endometrial adenocarcinoma has, to our knowledge, not yet been reported.…”

Section: Discussionmentioning

confidence: 83%

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

Nordengren

Lidebring

Bendahl

et al. 2001

Intl Journal of Cancer

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Previous studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI-2) and patient survival. High tumor tissue concentrations of PAI-2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI-1 have more consistently been associated with poor histologic differentiation and poor prognosis. Our study quantified PAI-2 and uPAR using specific enzyme-linked immunosorbent assays in homogenates of 274 samples of endometrial cancer tissue. The prognostic power of each factor was analyzed in the subgroup of patients with early stage disease, i.e., International Federation of Gynecology and Oncology (FIGO) surgical stage I-II (n ‫؍‬ 188). This group had a median follow-up time of 6.8 years (range 0.7-9.9), and 23 progressions were observed. The 80 th percentile for PAI-2 and uPAR was used to dichotomize the material, and the results were analyzed for associations with clinical data including progression-free survival. The results were also compared with DNA ploidy status, S-phase fraction, uPA and PAI-1, which we reported in a previous study (Fredstorp Lidebring et al., Eur J Cancer 2001; in press). A high PAI-2 level was associated with shorter progression-free survival in univariate analysis and was an independent prognostic factor in bivariate analyses, which included PAI-1, uPA and DNA ploidy status. In contrast, a high level of uPAR had no association with prognosis in early stage endometrial cancer. The combination of high PAI-2 and PAI-1 levels in tumors revealed a small group of stage I-II patients with an accumulative progression rate of 50%.

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Section: Discussionmentioning

confidence: 83%

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

Nordengren

Lidebring

Bendahl

et al. 2001

Intl Journal of Cancer

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“…Activated protein C counteracts the coagulation cascade by inactivation of factors Va and VIIIa. u-PA is a fibrinolytic agent that is expressed by endometrial tissue and has been shown to increase in normal premenstrual and menstrual endometrial tissue (25,26). PAI-1 modulates the activity of u-PA, and higher levels are normally expressed in menstrual phase endometrium (21)(22)(23).…”

Section: Tgf-␤3 Also Regulates Hemostatic Factors In Escmentioning

confidence: 99%

“…PAI-1 mRNA is normally localized in the walls of small vessels; however, the protein is also expressed in the stroma near to small blood vessels (26,27). In the late secretory and menstrual phases, PAI-1 mRNA and protein increase in stromal cells around the vessels and beneath the luminal epithelium (20,21).…”

Section: Tgf-␤3 Also Regulates Hemostatic Factors In Escmentioning

confidence: 99%

“…The endometrial release of plasminogen activator (PA) activity in uterine fluid increases during the proliferative phase to a maximum at midcycle, is low in the secretory phase, and then increases again premenstrually (18 -21). PA inhibitor 1 (PAI-1), a fibrinolytic modulator that binds to urokinase PA (u-PA), increases from the late proliferative phase, through the secretory phase, to a maximum in the menstrual phase (22)(23)(24)(25)(26). This pattern of gene expression contributes to the hemostatic mechanisms that allow normal menstrual blood flow in the normal uterus.…”

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confidence: 99%

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Leiomyoma Simultaneously Impair Endometrial BMP-2-Mediated Decidualization and Anticoagulant Expression through Secretion of TGF-β3

Sinclair

Mastroyannis

Taylor

2011

The Journal of Clinical Endocrinology &Amp; Metabolism

126

127

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“…SERPINB2 [8] and SERPINE1 [7,8] were demonstrated to be present in the human endometrium. SERPINE1 was even detected in human and mouse uteri during implantation [10,11], indicating that the PA inhibitor is involved in implantation.…”

Section: Introductionmentioning

confidence: 99%

SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase

Lee

Fan

Hwu

et al. 2011

Reprod Biol Endocrinol

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Background: SERPINE2, also known as protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent SERPINs that modulates the activity of plasminogen activators (PAs). PAs and their SERPIN inhibitors, such as SERPINB2 and SERPINE1, were expressed in the human endometrium and were implicated in implantation. However, expression data about SERPINE2 in the human endometrium is still unknown. Thus, we conducted an investigation to reveal the spatiotemporal and cellular expression of SERPINE2 in the human uterus during the menstrual cycle. Methods: Seven patients who underwent a hysterectomy and samples of 120 archived patients' endometrial curettage or parts of the uterus that were formalin-fixed and embedded in paraffin. Western blotting was performed to evaluate the specificity and sensitivity of the antibody. Immunohistochemistry was conducted to localize the SERPINE2 expression site. Quantitative analysis was conducted to evaluate expression levels of SERPINE2 in various sub-phases of the menstrual cycle. Results: The SERPINE2 protein was primarily detected in the uterine fluid during the mid-and late-secretory phases of the menstrual cycle. It was predominantly expressed in the luminal and glandular epithelium, less in the myometrium, and only dispersedly in certain stromal cells throughout the menstrual cycle. A quantitative analysis of expression levels of SERPINE2 in the glandular epithelium revealed that it was highly expressed in the endometrium during the secretory phase compared to the proliferative phase. Conclusions: The SERPINE2 protein is highly expressed in the endometrium during the secretory phase, indicating that it may participate in tissue remodeling involved in implantation.

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Plasminogen activator inhibitor 2 in menstrual endometrium and in primary cultures of endometrial cells

Cited by 6 publications

References 29 publications

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

High tumor tissue concentration of plasminogen activator inhibitor 2 (PAI‐2) is an independent marker for shorter progression‐free survival in patients with early stage endometrial cancer

Leiomyoma Simultaneously Impair Endometrial BMP-2-Mediated Decidualization and Anticoagulant Expression through Secretion of TGF-β3

SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase

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