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Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/β-Catenin Signaling.

Qi L, Song W, Liu Z, Zhao X, Cao W, Sun B - Int J Mol Sci (2015)

Bottom Line: Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation.However, the functions of canonical Wnt signaling in VM formation have not yet been explored.In addition, the Wnt/β-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. qilisha2005@163.com.

ABSTRACT
Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation. However, the functions of canonical Wnt signaling in VM formation have not yet been explored. In this study, we found the presence of VM was related to colon cancer histological differentiation (p < 0.001), the clinical stage (p < 0.001), and presence of metastasis and recurrence (p < 0.001). VM-positive colon cancer samples showed increased Wnt3a expression (p < 0.001) and β-catenin nuclear expression (p < 0.001) compared with the VM-negative samples. In vitro, over-regulated Wnt3a expression in HT29 colon cancer cells promoted the capacity to form tube-like structures in the three-dimensional (3-D) culture together with increased expression of endothelial phenotype-associated proteins such as VEGFR2 and VE-cadherin. The mouse xenograft model showed that Wnt3a-overexpressing cells grew into larger tumor masses and formed more VM than the control cells. In addition, the Wnt/β-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells. Taken together, our results suggest that Wnt/β-catenin signaling is involved in VM formation in colon cancer and might contribute to the development of more accurate treatment modalities aimed at VM.

No MeSH data available.


Related in: MedlinePlus

Wnt3a promoted the VM-forming ability in HT29 cells. (A) HT29 cells cannot form typical tube-like structures in the 3D culture, whereas Wnt3a-overexpressing clone9 and clone20 cells formed few tubular structures (red arrows). Scale bar: 100 μm; (B) Upregulated Wnt3a expression in HT29 cells results in increased VEGFR2 and VE-cadherin expressions. No significant change in VEGFR1 expression was observed (left) (* p < 0.05). Relative amount of protein expression of VEGFR1, VEGFR2, and VE-cadherin compared with β-actin (right); (C) Representative xenograft tumors of the control or Wnt3a-overexpressing HT29 cells (clone9) on the 30th day post injection (left). Tumor volumes are monitored over time (right); (D) VM structure and endothelial-dependent vessels in xenograft tumors (CD34/PAS double staining, ×400).
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ijms-16-18564-f004: Wnt3a promoted the VM-forming ability in HT29 cells. (A) HT29 cells cannot form typical tube-like structures in the 3D culture, whereas Wnt3a-overexpressing clone9 and clone20 cells formed few tubular structures (red arrows). Scale bar: 100 μm; (B) Upregulated Wnt3a expression in HT29 cells results in increased VEGFR2 and VE-cadherin expressions. No significant change in VEGFR1 expression was observed (left) (* p < 0.05). Relative amount of protein expression of VEGFR1, VEGFR2, and VE-cadherin compared with β-actin (right); (C) Representative xenograft tumors of the control or Wnt3a-overexpressing HT29 cells (clone9) on the 30th day post injection (left). Tumor volumes are monitored over time (right); (D) VM structure and endothelial-dependent vessels in xenograft tumors (CD34/PAS double staining, ×400).

Mentions: Three-dimensional culture is used to effectively test not only the vascular behavior of endothelial cells but also the ability of a number of tumor cells to form VM structures. We showed that HT29 cells cannot form tubular structures, whereas Wnt3a-overexpression HT29 cells (clone9 and clone20) formed few tubular structures, thereby indicating that Wnt3a may be an activator for VM formation in HT29 cells (Figure 4A).


Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/β-Catenin Signaling.

Qi L, Song W, Liu Z, Zhao X, Cao W, Sun B - Int J Mol Sci (2015)

Wnt3a promoted the VM-forming ability in HT29 cells. (A) HT29 cells cannot form typical tube-like structures in the 3D culture, whereas Wnt3a-overexpressing clone9 and clone20 cells formed few tubular structures (red arrows). Scale bar: 100 μm; (B) Upregulated Wnt3a expression in HT29 cells results in increased VEGFR2 and VE-cadherin expressions. No significant change in VEGFR1 expression was observed (left) (* p < 0.05). Relative amount of protein expression of VEGFR1, VEGFR2, and VE-cadherin compared with β-actin (right); (C) Representative xenograft tumors of the control or Wnt3a-overexpressing HT29 cells (clone9) on the 30th day post injection (left). Tumor volumes are monitored over time (right); (D) VM structure and endothelial-dependent vessels in xenograft tumors (CD34/PAS double staining, ×400).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581260&req=5

ijms-16-18564-f004: Wnt3a promoted the VM-forming ability in HT29 cells. (A) HT29 cells cannot form typical tube-like structures in the 3D culture, whereas Wnt3a-overexpressing clone9 and clone20 cells formed few tubular structures (red arrows). Scale bar: 100 μm; (B) Upregulated Wnt3a expression in HT29 cells results in increased VEGFR2 and VE-cadherin expressions. No significant change in VEGFR1 expression was observed (left) (* p < 0.05). Relative amount of protein expression of VEGFR1, VEGFR2, and VE-cadherin compared with β-actin (right); (C) Representative xenograft tumors of the control or Wnt3a-overexpressing HT29 cells (clone9) on the 30th day post injection (left). Tumor volumes are monitored over time (right); (D) VM structure and endothelial-dependent vessels in xenograft tumors (CD34/PAS double staining, ×400).
Mentions: Three-dimensional culture is used to effectively test not only the vascular behavior of endothelial cells but also the ability of a number of tumor cells to form VM structures. We showed that HT29 cells cannot form tubular structures, whereas Wnt3a-overexpression HT29 cells (clone9 and clone20) formed few tubular structures, thereby indicating that Wnt3a may be an activator for VM formation in HT29 cells (Figure 4A).

Bottom Line: Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation.However, the functions of canonical Wnt signaling in VM formation have not yet been explored.In addition, the Wnt/β-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. qilisha2005@163.com.

ABSTRACT
Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation. However, the functions of canonical Wnt signaling in VM formation have not yet been explored. In this study, we found the presence of VM was related to colon cancer histological differentiation (p < 0.001), the clinical stage (p < 0.001), and presence of metastasis and recurrence (p < 0.001). VM-positive colon cancer samples showed increased Wnt3a expression (p < 0.001) and β-catenin nuclear expression (p < 0.001) compared with the VM-negative samples. In vitro, over-regulated Wnt3a expression in HT29 colon cancer cells promoted the capacity to form tube-like structures in the three-dimensional (3-D) culture together with increased expression of endothelial phenotype-associated proteins such as VEGFR2 and VE-cadherin. The mouse xenograft model showed that Wnt3a-overexpressing cells grew into larger tumor masses and formed more VM than the control cells. In addition, the Wnt/β-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells. Taken together, our results suggest that Wnt/β-catenin signaling is involved in VM formation in colon cancer and might contribute to the development of more accurate treatment modalities aimed at VM.

No MeSH data available.


Related in: MedlinePlus