Demonstration of inducible TFPI-2 mRNA synthesis in BeWo and JEG-3 trophoblast cells using a competitive RT-PCR

Iochmann, Sophie; Reverdiau-Moalic, P; Hubé, Florent; Bardos, P.; Gruel, Yves

doi:10.1016/s0049-3848(02)00018-x

Cited by 13 publications

(14 citation statements)

References 45 publications

(49 reference statements)

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“…Real-time PCR is a sensitive and reproducible method that represents a significant advance for the analysis of TFPI-2 gene expression compared to Northern blot analysis (Izumi et al, 2000), semiquantitative RT -PCR (Iochmann et al, 1999) and competitive RT -PCR (Iochmann et al, 2002). In particular, this procedure allowed us to detect significant levels of TFPI-2 mRNA in noncancerous lung tissue, whereas such expression had not been previously demonstrated by RNA blot hybridisation (Izumi et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer

et al. 2005

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Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor that inhibits plasmin-dependent activation of several metalloproteinases. Downregulation of TFPI-2 could thus enhance the invasive potential of neoplastic cells in several cancers, including lung cancer. In this study, TFPI-2 mRNA was measured using a real-time PCR method in tumours of 59 patients with nonsmall-cell lung cancer (NSCLC). Tumour TFPI-2 mRNA levels appeared well correlated with protein expression evaluated by immunohistochemistry and were 4 -120 times lower compared to those of nonaffected lung tissue in 22 cases (37%). Hypermethylation of the TFPI-2 gene promoter was demonstrated by restriction enzyme-polymerase chain reaction in 12 of 40 cases of NSCLC (30%), including nine of 17 for whom tumour TFPI-2 gene expression was lower than in noncancerous tissue. In contrast, this epigenetic modification was shown in only three of 23 tumours in which no decrease in TFPI-2 synthesis was found (P ¼ 0.016). Decreased TFPI-2 gene expression and hypermethylation were more frequently associated with stages III or IV NSCLC (eight out of 10, P ¼ 0.02) and the TFPI-2 gene promoter was more frequently hypermethylated in patients with lymph node metastases (eight out of 16, P ¼ 0.02). These results suggest that silencing of the TFPI-2 gene by hypermethylation might contribute to tumour progression in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer

et al. 2005

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“…TFPI‐2 is a 32 kD Kunitz‐type serine proteinase inhibitor secreted into the ECM by a wide variety of human cells including endothelial cells, monocytes, fibroblasts, epithelial cells, smooth muscle cells, syncytiotrophoblast cells [8–11] and also several human tumour cells [12–15]. Interestingly, TFPI‐2, now considered to be a candidate tumour suppressor gene, has been shown to be down‐regulated in particularly aggressive tumours [11, 13, 16] in association with epigenetic changes.…”

Section: Introductionmentioning

confidence: 99%

“…Apart from tissue inhibitors of metalloproteinases (TIMPs) that are specific regulators of MMP activity, TFPI-2 (tissue factor pathway inhibitor-2), an inhibitor of serine proteases -particularly plasmin -could also regulate the activation of MMPs [6,7], thus regulating ECM degradation and tumour cell invasion. TFPI-2 is a 32 kD Kunitz-type serine proteinase inhibitor secreted into the ECM by a wide variety of human cells including endothelial cells, monocytes, fibroblasts, epithelial cells, smooth muscle cells, syncytiotrophoblast cells [8][9][10][11] and also several human tumour cells [12][13][14][15]. Interestingly, TFPI-2, now considered to be a candidate tumour suppressor gene, has been shown to be down-regulated in particularly aggressive tumours [11,13,16] in association with epigenetic changes.…”

Section: Introductionmentioning

confidence: 99%

TFPI-2 silencing increases tumour progression and promotes metalloproteinase 1 and 3 induction through tumour-stromal cell interactions

Gaud¹,

Iochmann²,

Guillon-Munos³

et al. 2011

Journal of Cellular and Molecular Medicine

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Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin which activates matrix metalloproteinases (MMPs) involved in degradation of the extracellular matrix. Its secretion in the tumour microenvironment makes TFPI-2 a potential inhibitor of tumour invasion and metastasis. As demonstrated in aggressive cancers, TFPI-2 is frequently down-regulated in cancer cells, but the mechanisms involved in the inhibition of tumour progression remained unclear. We showed in this study that stable TFPI-2 down-regulation in the National Cancer Institute (NCI)-H460 non-small cell lung cancer cell line using specific micro interfering micro-interfering RNA promoted tumour progression in a nude mice orthotopic model that resulted in an increase in cell invasion. Moreover, TFPI-2 down-regulation enhanced cell adhesion to collagen IV and laminin via an increase in α1 integrin on cell surface, and increased MMP expression (mainly MMP-1 and -3) contributing to cancer cell invasion through basement membrane components. This study also reveals for the first time that pulmonary fibroblasts incubated with conditioned media from TFPI-2 silencing cancer cells exhibited increased expression of MMPs, particularly MMP-1, -3 and -7, that are likely involved in lung cancer cell invasion through the surrounding stromal tissue, thus enhancing formation of metastases.

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“…TFPI-2 is secreted into the ECM (extracellular matrix) by a wide variety of human cells, including endothelial cells [1], monocytes [2], fibroblasts [3], epithelial cells [4], smooth muscle cells [5], syncytiotrophoblast cells [6,7], and several human tumour cells [8][9][10][11]. TFPI-2 is secreted into the ECM (extracellular matrix) by a wide variety of human cells, including endothelial cells [1], monocytes [2], fibroblasts [3], epithelial cells [4], smooth muscle cells [5], syncytiotrophoblast cells [6,7], and several human tumour cells [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

The interaction of the second Kunitz-type domain (KD2) of TFPI-2 with a novel interaction partner, prosaposin, mediates the inhibition of the invasion and migration of human fibrosarcoma cells

Deng

Mao

et al. 2011

Biochemical Journal

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TFPI-2 (tissue factor pathway inhibitor-2) has recently been recognized as a new tumour suppressor gene. Low expression of this protein in several types of cancers allows for enhanced tumour growth, invasion and metastasis. To investigate the molecular mechanism responsible for the tumour-suppressor effects of TFPI-2, we performed yeast two-hybrid analysis and identified PSAP (prosaposin) as a TFPI-2-interacting partner. This interaction was confirmed by co-immunoprecipitation and immunofluorescence. The region of TFPI-2 that interacts with PSAP is located in the KD2 (Kunitz-type domain 2). Further study showed that PSAP does not affect the function of TFPI-2 as a serine proteinase inhibitor, but that TFPI-2 could inhibit the invasion-promoting effects of PSAP in human HT1080 fibrosarcoma cells. The results of the present study revealed that TFPI-2 interacts with PSAP, which may play an important role in the physiology and pathology of diseases such as cancer.

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Demonstration of inducible TFPI-2 mRNA synthesis in BeWo and JEG-3 trophoblast cells using a competitive RT-PCR

Cited by 13 publications

References 45 publications

Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer

Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer

TFPI-2 silencing increases tumour progression and promotes metalloproteinase 1 and 3 induction through tumour-stromal cell interactions

The interaction of the second Kunitz-type domain (KD2) of TFPI-2 with a novel interaction partner, prosaposin, mediates the inhibition of the invasion and migration of human fibrosarcoma cells

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