Limits...
Expression of platelet-derived growth factor receptor β is maintained by Prox1 in lymphatic endothelial cells and is required for tumor lymphangiogenesis.

Miyazaki H, Yoshimatsu Y, Akatsu Y, Mishima K, Fukayama M, Watabe T, Miyazono K - Cancer Sci. (2014)

Bottom Line: Furthermore, we found that PDGF signals play important roles in inflammatory lymphangiogenesis in a chronic aseptic peritonitis model.Intraperitoneal administration of imatinib, a potent inhibitor of PDGFRβ, and transduction of PDGFRβ/Fc chimeric protein by an adenoviral system both reduced inflammatory lymphangiogenesis induced by thioglycollate in mice.We also found that the expression of PDGFRβ/Fc reduced tumor lymphangiogenesis in a BxPC3 human pancreatic cancer xenograft model.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Show MeSH

Related in: MedlinePlus

Roles of endogenous Prox1 expression in human dermal lymphatic endothelial cells (HDLECs) in the maintenance of platelet-derived growth factor receptor (PDGFR) β expression and their migration to PDGF-BB. (a, b) HDLECs were transfected with negative control siRNA (siNC) or specific siRNA for Prox1 (siProx1), and were subjected to quantitative RT-PCR analyses for the expression of Prox1 (a) and PDGFRβ (b) and Western blot analysis (c) for PDGFRb (top) and Prox1 (middle) and α-tubulin (bottom). (d) Effects of Prox1 knockdown on the chemotaxis of HDLECs towards PDGF-BB. Cell migration was measured by Boyden chamber. HDLECs were transfected with scrambled siRNAs (siNC) or Prox1 siRNAs (siProx1) and plated on the upper chambers, with PDGF-BB (100 ng/mL) placed in the lower chambers. Results were expressed as the ratio of number of migrated cells normalized to control (no PDGF-BB). Each value represents the mean of triplicate determinations. Error bars represent SD. **P < 0.01. N.S., not significant (evaluated by Student's t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4462385&req=5

fig04: Roles of endogenous Prox1 expression in human dermal lymphatic endothelial cells (HDLECs) in the maintenance of platelet-derived growth factor receptor (PDGFR) β expression and their migration to PDGF-BB. (a, b) HDLECs were transfected with negative control siRNA (siNC) or specific siRNA for Prox1 (siProx1), and were subjected to quantitative RT-PCR analyses for the expression of Prox1 (a) and PDGFRβ (b) and Western blot analysis (c) for PDGFRb (top) and Prox1 (middle) and α-tubulin (bottom). (d) Effects of Prox1 knockdown on the chemotaxis of HDLECs towards PDGF-BB. Cell migration was measured by Boyden chamber. HDLECs were transfected with scrambled siRNAs (siNC) or Prox1 siRNAs (siProx1) and plated on the upper chambers, with PDGF-BB (100 ng/mL) placed in the lower chambers. Results were expressed as the ratio of number of migrated cells normalized to control (no PDGF-BB). Each value represents the mean of triplicate determinations. Error bars represent SD. **P < 0.01. N.S., not significant (evaluated by Student's t-test).

Mentions: Next, in order to examine whether Prox1 is involved in the PDGFRβ expression in HDLECs, we studied the effects of knockdown of Prox1 expression in HDLECs on PDGFRβ expression and their characteristics. When the levels of endogenous Prox1 expression were decreased by siRNA (Fig.4a), the expression levels of PDGFRβ as well as those of VEGFR3 and podoplanin were decreased (Fig.4b, unpublished data), which was confirmed at a protein level (Fig.4c). These results suggest that Prox1 maintains the expression of PDGFRβ in HDLECs.


Expression of platelet-derived growth factor receptor β is maintained by Prox1 in lymphatic endothelial cells and is required for tumor lymphangiogenesis.

Miyazaki H, Yoshimatsu Y, Akatsu Y, Mishima K, Fukayama M, Watabe T, Miyazono K - Cancer Sci. (2014)

Roles of endogenous Prox1 expression in human dermal lymphatic endothelial cells (HDLECs) in the maintenance of platelet-derived growth factor receptor (PDGFR) β expression and their migration to PDGF-BB. (a, b) HDLECs were transfected with negative control siRNA (siNC) or specific siRNA for Prox1 (siProx1), and were subjected to quantitative RT-PCR analyses for the expression of Prox1 (a) and PDGFRβ (b) and Western blot analysis (c) for PDGFRb (top) and Prox1 (middle) and α-tubulin (bottom). (d) Effects of Prox1 knockdown on the chemotaxis of HDLECs towards PDGF-BB. Cell migration was measured by Boyden chamber. HDLECs were transfected with scrambled siRNAs (siNC) or Prox1 siRNAs (siProx1) and plated on the upper chambers, with PDGF-BB (100 ng/mL) placed in the lower chambers. Results were expressed as the ratio of number of migrated cells normalized to control (no PDGF-BB). Each value represents the mean of triplicate determinations. Error bars represent SD. **P < 0.01. N.S., not significant (evaluated by Student's t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4462385&req=5

fig04: Roles of endogenous Prox1 expression in human dermal lymphatic endothelial cells (HDLECs) in the maintenance of platelet-derived growth factor receptor (PDGFR) β expression and their migration to PDGF-BB. (a, b) HDLECs were transfected with negative control siRNA (siNC) or specific siRNA for Prox1 (siProx1), and were subjected to quantitative RT-PCR analyses for the expression of Prox1 (a) and PDGFRβ (b) and Western blot analysis (c) for PDGFRb (top) and Prox1 (middle) and α-tubulin (bottom). (d) Effects of Prox1 knockdown on the chemotaxis of HDLECs towards PDGF-BB. Cell migration was measured by Boyden chamber. HDLECs were transfected with scrambled siRNAs (siNC) or Prox1 siRNAs (siProx1) and plated on the upper chambers, with PDGF-BB (100 ng/mL) placed in the lower chambers. Results were expressed as the ratio of number of migrated cells normalized to control (no PDGF-BB). Each value represents the mean of triplicate determinations. Error bars represent SD. **P < 0.01. N.S., not significant (evaluated by Student's t-test).
Mentions: Next, in order to examine whether Prox1 is involved in the PDGFRβ expression in HDLECs, we studied the effects of knockdown of Prox1 expression in HDLECs on PDGFRβ expression and their characteristics. When the levels of endogenous Prox1 expression were decreased by siRNA (Fig.4a), the expression levels of PDGFRβ as well as those of VEGFR3 and podoplanin were decreased (Fig.4b, unpublished data), which was confirmed at a protein level (Fig.4c). These results suggest that Prox1 maintains the expression of PDGFRβ in HDLECs.

Bottom Line: Furthermore, we found that PDGF signals play important roles in inflammatory lymphangiogenesis in a chronic aseptic peritonitis model.Intraperitoneal administration of imatinib, a potent inhibitor of PDGFRβ, and transduction of PDGFRβ/Fc chimeric protein by an adenoviral system both reduced inflammatory lymphangiogenesis induced by thioglycollate in mice.We also found that the expression of PDGFRβ/Fc reduced tumor lymphangiogenesis in a BxPC3 human pancreatic cancer xenograft model.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Human Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus