Abstract
Background Induction of epithelial-mesenchymal transition (EMT) is essential for the metastasis of tumor cells and maintaining their stemness. This study aimed to examine whether endothelial cells, which are most closely located to tumor cells in vivo, play a role in inducing EMT in tumor cells or not. Methods Concentrated culture medium of bovine aortic endothelial cells (BAECs) was applied to tumor cell lines (A549 and PANC-1) and epithelial cell line (NMuMg). Cadherin conversion, expressions of α-smooth muscle actin and ZO-1, actin fiber formation and cell migration were examined as hallmarks of the induction of EMT in these cell lines. Transforming growth factor β (TGFβ) antibodies were used to neutralize TGFβ1, TGFβ2 and TGFβ3. Expression and release of TGFβ proteins in BAECs as well as in porcine and human endothelial cells were assessed by Western blotting and ELISA, respectively. Results Conditioned medium of BAEC induced EMT in the examined cell lines. All endothelial cells from various species and locations expressed TGFβ1 and TGFβ2 proteins and much lower level of TGFβ3 protein. Conditioned medium from these endothelial cells contained TGFβ1 and TGFβ2, but TGFβ3 could not be detected. Neutralizing antibody against each of TGFβ1 or TGFβ2 did not reverse endothelium-dependent EMT, but simultaneous neutralization of both TGFβ1 and TGFβ2 completely abolished it. Conclusions Endothelial cells may play a role in the induction and maintenance of EMT in tumor cells by constitutively releasing TGFβ1 and TGFβ2. General significance The present results provide a novel strategy of the inhibition of tumor metastasis by targeting vascular endothelium.
| Original language | English |
|---|---|
| Pages (from-to) | 4470-4481 |
| Number of pages | 12 |
| Journal | Biochimica et Biophysica Acta - General Subjects |
| Volume | 1830 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Jul 3 2013 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
Cite this
Endothelium-dependent epithelial-mesenchymal transition of tumor cells : Exclusive roles of transforming growth factor β1 and β2. / Kimura, Chiwaka; Hayashi, Masayuki; Mizuno, Yuri; Oike, Masahiro.
In: Biochimica et Biophysica Acta - General Subjects, Vol. 1830, No. 10, 03.07.2013, p. 4470-4481.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endothelium-dependent epithelial-mesenchymal transition of tumor cells
T2 - Exclusive roles of transforming growth factor β1 and β2
AU - Kimura, Chiwaka
AU - Hayashi, Masayuki
AU - Mizuno, Yuri
AU - Oike, Masahiro
PY - 2013/7/3
Y1 - 2013/7/3
N2 - Background Induction of epithelial-mesenchymal transition (EMT) is essential for the metastasis of tumor cells and maintaining their stemness. This study aimed to examine whether endothelial cells, which are most closely located to tumor cells in vivo, play a role in inducing EMT in tumor cells or not. Methods Concentrated culture medium of bovine aortic endothelial cells (BAECs) was applied to tumor cell lines (A549 and PANC-1) and epithelial cell line (NMuMg). Cadherin conversion, expressions of α-smooth muscle actin and ZO-1, actin fiber formation and cell migration were examined as hallmarks of the induction of EMT in these cell lines. Transforming growth factor β (TGFβ) antibodies were used to neutralize TGFβ1, TGFβ2 and TGFβ3. Expression and release of TGFβ proteins in BAECs as well as in porcine and human endothelial cells were assessed by Western blotting and ELISA, respectively. Results Conditioned medium of BAEC induced EMT in the examined cell lines. All endothelial cells from various species and locations expressed TGFβ1 and TGFβ2 proteins and much lower level of TGFβ3 protein. Conditioned medium from these endothelial cells contained TGFβ1 and TGFβ2, but TGFβ3 could not be detected. Neutralizing antibody against each of TGFβ1 or TGFβ2 did not reverse endothelium-dependent EMT, but simultaneous neutralization of both TGFβ1 and TGFβ2 completely abolished it. Conclusions Endothelial cells may play a role in the induction and maintenance of EMT in tumor cells by constitutively releasing TGFβ1 and TGFβ2. General significance The present results provide a novel strategy of the inhibition of tumor metastasis by targeting vascular endothelium.
AB - Background Induction of epithelial-mesenchymal transition (EMT) is essential for the metastasis of tumor cells and maintaining their stemness. This study aimed to examine whether endothelial cells, which are most closely located to tumor cells in vivo, play a role in inducing EMT in tumor cells or not. Methods Concentrated culture medium of bovine aortic endothelial cells (BAECs) was applied to tumor cell lines (A549 and PANC-1) and epithelial cell line (NMuMg). Cadherin conversion, expressions of α-smooth muscle actin and ZO-1, actin fiber formation and cell migration were examined as hallmarks of the induction of EMT in these cell lines. Transforming growth factor β (TGFβ) antibodies were used to neutralize TGFβ1, TGFβ2 and TGFβ3. Expression and release of TGFβ proteins in BAECs as well as in porcine and human endothelial cells were assessed by Western blotting and ELISA, respectively. Results Conditioned medium of BAEC induced EMT in the examined cell lines. All endothelial cells from various species and locations expressed TGFβ1 and TGFβ2 proteins and much lower level of TGFβ3 protein. Conditioned medium from these endothelial cells contained TGFβ1 and TGFβ2, but TGFβ3 could not be detected. Neutralizing antibody against each of TGFβ1 or TGFβ2 did not reverse endothelium-dependent EMT, but simultaneous neutralization of both TGFβ1 and TGFβ2 completely abolished it. Conclusions Endothelial cells may play a role in the induction and maintenance of EMT in tumor cells by constitutively releasing TGFβ1 and TGFβ2. General significance The present results provide a novel strategy of the inhibition of tumor metastasis by targeting vascular endothelium.
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UR - http://www.scopus.com/inward/citedby.url?scp=84879473149&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2013.05.009
DO - 10.1016/j.bbagen.2013.05.009
M3 - Article
C2 - 23668958
AN - SCOPUS:84879473149
VL - 1830
SP - 4470
EP - 4481
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
SN - 0304-4165
IS - 10
ER -