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

Gaud G, Iochmann S, Guillon-Munos A, Brillet B, Petiot S, Seigneuret F, Touzé A, Heuzé-Vourc'h N, Courty Y, Lerondel S, Gruel Y, Reverdiau P - J. Cell. Mol. Med. (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Inserm, U618, Université François Rabelais, Tours, France.

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Identification of signal transduction pathway involved when TFPI-2 is down-regulated in lung cancer cells. Using a luciferase pathway reporter array, the firefly luciferase activity of inducible transcription factor-responsive construct transfected in miRNA clones was measured and related to Renilla luciferase activity of constitutively expressing Renilla luciferase construct measured in the same cells for normalizing transfection efficiencies. Results represent the mean ± S.E.M. of experiments performed with miRNA-Neg clone, miRNA-1b and miRNA-2b clone (n= 7). (*P < 0.05, compared with the miRNA-Neg clone, Student t-test).
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fig06: Identification of signal transduction pathway involved when TFPI-2 is down-regulated in lung cancer cells. Using a luciferase pathway reporter array, the firefly luciferase activity of inducible transcription factor-responsive construct transfected in miRNA clones was measured and related to Renilla luciferase activity of constitutively expressing Renilla luciferase construct measured in the same cells for normalizing transfection efficiencies. Results represent the mean ± S.E.M. of experiments performed with miRNA-Neg clone, miRNA-1b and miRNA-2b clone (n= 7). (*P < 0.05, compared with the miRNA-Neg clone, Student t-test).

Mentions: To determine whether various signalling pathways were activated in TFPI-2 down-regulated non-small lung cancer cells, we measured the activities of 10 signal transduction pathways involved in cancer biology using a dual-luciferase reporter assay. As shown in Fig. 6, an increase in relative luciferase activity was observed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and NF-κB pathways in NCI-H460 clones when compared to negative control. In addition, down-regulation of TFPI-2 in miRNA-1b and -2b clones was also associated with a slight increase in NF-κB pathway (P > 0.05) and a significant increase in the ERK and JNK pathways compared to the miRNA-Neg clone (P < 0.05). Other signalling pathway activities remained unchanged in all NCI-H460 clones compared to negative control.


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

Gaud G, Iochmann S, Guillon-Munos A, Brillet B, Petiot S, Seigneuret F, Touzé A, Heuzé-Vourc'h N, Courty Y, Lerondel S, Gruel Y, Reverdiau P - J. Cell. Mol. Med. (2011)

Identification of signal transduction pathway involved when TFPI-2 is down-regulated in lung cancer cells. Using a luciferase pathway reporter array, the firefly luciferase activity of inducible transcription factor-responsive construct transfected in miRNA clones was measured and related to Renilla luciferase activity of constitutively expressing Renilla luciferase construct measured in the same cells for normalizing transfection efficiencies. Results represent the mean ± S.E.M. of experiments performed with miRNA-Neg clone, miRNA-1b and miRNA-2b clone (n= 7). (*P < 0.05, compared with the miRNA-Neg clone, Student t-test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822788&req=5

fig06: Identification of signal transduction pathway involved when TFPI-2 is down-regulated in lung cancer cells. Using a luciferase pathway reporter array, the firefly luciferase activity of inducible transcription factor-responsive construct transfected in miRNA clones was measured and related to Renilla luciferase activity of constitutively expressing Renilla luciferase construct measured in the same cells for normalizing transfection efficiencies. Results represent the mean ± S.E.M. of experiments performed with miRNA-Neg clone, miRNA-1b and miRNA-2b clone (n= 7). (*P < 0.05, compared with the miRNA-Neg clone, Student t-test).
Mentions: To determine whether various signalling pathways were activated in TFPI-2 down-regulated non-small lung cancer cells, we measured the activities of 10 signal transduction pathways involved in cancer biology using a dual-luciferase reporter assay. As shown in Fig. 6, an increase in relative luciferase activity was observed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and NF-κB pathways in NCI-H460 clones when compared to negative control. In addition, down-regulation of TFPI-2 in miRNA-1b and -2b clones was also associated with a slight increase in NF-κB pathway (P > 0.05) and a significant increase in the ERK and JNK pathways compared to the miRNA-Neg clone (P < 0.05). Other signalling pathway activities remained unchanged in all NCI-H460 clones compared to negative control.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Inserm, U618, Université François Rabelais, Tours, France.

Show MeSH
Related in: MedlinePlus