Limits...
Vasohibin-1 suppresses colon cancer.

Liu S, Han B, Zhang Q, Dou J, Wang F, Lin W, Sun Y, Peng G - Oncotarget (2015)

Bottom Line: Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients.Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo.In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Jinan Central Hospital, Affiliated to Shandong University, Jinan, P. R. China.

ABSTRACT
Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

No MeSH data available.


Related in: MedlinePlus

Knockdown of VASH1 in human colon cancer HCT116 cells promoted tumor tumorigenesis and metastasis in vivo(A) Knockdown of VASH1 in HCT116 cells dramatically promoted tumor growth in Rag1−/− immunodeficient mice. (B) Representative image of the xenograft tumors shown are obtained from the two groups at the endpoint of the experiments (day 33). (C) The mean weights of xenograft tumors obtained from the two groups at the endpoint of the experiments (day 33). Human colon cancer HCT116 cells (4 × 106/mouse) transfected with VASH1 shRNA or control shRNA, were subcutaneously injected into Rag1−/− mice (n=5). Tumor growth was evaluated (in F). At the end of experiments, tumors were isolated from the sacrificed mice and weighted (G). *p<0.05 compared with the control shRNA group (G). (D) Knockdown of VASH1 in HCT116 cells significantly increased Ki-67+ cell populations compared with control shRNA group in the tumor tissues. Tumor tissue sections were determined for Ki-67 expression using the immunohistochemical staining. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (E) Knockdown of VASH1 in HCT116 cells dramatically increased tumor macrometastatic numbers in lung and liver surfaces. Human colon cancer HCT116 cells (2 × 106/mouse) transfected with VASH1-specific or control shRNA were injected tail intravenously into Rag1−/− mice. Livers and lungs were harvested from the mice of different groups at 6 weeks post injection, and tumor metastases determined. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (F) H & E staining on sections from embedded lung and liver tissues showed that high amount of tumor cells infiltrated into lungs and livers obtained from VASH1 shRNA treatment group, but not from the control shRNA treatment group. Tumor metastatic spots were indicated by the arrows.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4480723&req=5

Figure 7: Knockdown of VASH1 in human colon cancer HCT116 cells promoted tumor tumorigenesis and metastasis in vivo(A) Knockdown of VASH1 in HCT116 cells dramatically promoted tumor growth in Rag1−/− immunodeficient mice. (B) Representative image of the xenograft tumors shown are obtained from the two groups at the endpoint of the experiments (day 33). (C) The mean weights of xenograft tumors obtained from the two groups at the endpoint of the experiments (day 33). Human colon cancer HCT116 cells (4 × 106/mouse) transfected with VASH1 shRNA or control shRNA, were subcutaneously injected into Rag1−/− mice (n=5). Tumor growth was evaluated (in F). At the end of experiments, tumors were isolated from the sacrificed mice and weighted (G). *p<0.05 compared with the control shRNA group (G). (D) Knockdown of VASH1 in HCT116 cells significantly increased Ki-67+ cell populations compared with control shRNA group in the tumor tissues. Tumor tissue sections were determined for Ki-67 expression using the immunohistochemical staining. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (E) Knockdown of VASH1 in HCT116 cells dramatically increased tumor macrometastatic numbers in lung and liver surfaces. Human colon cancer HCT116 cells (2 × 106/mouse) transfected with VASH1-specific or control shRNA were injected tail intravenously into Rag1−/− mice. Livers and lungs were harvested from the mice of different groups at 6 weeks post injection, and tumor metastases determined. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (F) H & E staining on sections from embedded lung and liver tissues showed that high amount of tumor cells infiltrated into lungs and livers obtained from VASH1 shRNA treatment group, but not from the control shRNA treatment group. Tumor metastatic spots were indicated by the arrows.

Mentions: We also performed a parallel xenograft model to investigate whether knockdown of VASH1 in colon cancer cells can promote tumor growth and tumorigenesis. Human colon cancer HCT116 cells transfected with VASH1 shRNA or control shRNA, were subcutaneously injected into Rag1−/− mice. As shown in Figure 7A, knockdown of VASH1 in HCT116 cells dramatically promoted tumor growth, compared with the control shRNA–transfected HCT116 cells. In addition, tumor sizes collected from the VASH1 shRNA group on day 33 post inoculation were significantly larger than those in the control shRNA group (Figure 7B). Notably, the average tumor weights obtained from the VASH1 shRNA group also showed much higher than that of control shRNA group (Figure 7C). In addition, knockdown of VASH1 expression in HCT116 cells significantly increased Ki-67+ cell populations in the tumor tissues (Figure 7D). These data indicated that silence of VASH1 expression in tumor cells directly enhanced tumor growth and tumorigenesis in vivo.


Vasohibin-1 suppresses colon cancer.

Liu S, Han B, Zhang Q, Dou J, Wang F, Lin W, Sun Y, Peng G - Oncotarget (2015)

Knockdown of VASH1 in human colon cancer HCT116 cells promoted tumor tumorigenesis and metastasis in vivo(A) Knockdown of VASH1 in HCT116 cells dramatically promoted tumor growth in Rag1−/− immunodeficient mice. (B) Representative image of the xenograft tumors shown are obtained from the two groups at the endpoint of the experiments (day 33). (C) The mean weights of xenograft tumors obtained from the two groups at the endpoint of the experiments (day 33). Human colon cancer HCT116 cells (4 × 106/mouse) transfected with VASH1 shRNA or control shRNA, were subcutaneously injected into Rag1−/− mice (n=5). Tumor growth was evaluated (in F). At the end of experiments, tumors were isolated from the sacrificed mice and weighted (G). *p<0.05 compared with the control shRNA group (G). (D) Knockdown of VASH1 in HCT116 cells significantly increased Ki-67+ cell populations compared with control shRNA group in the tumor tissues. Tumor tissue sections were determined for Ki-67 expression using the immunohistochemical staining. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (E) Knockdown of VASH1 in HCT116 cells dramatically increased tumor macrometastatic numbers in lung and liver surfaces. Human colon cancer HCT116 cells (2 × 106/mouse) transfected with VASH1-specific or control shRNA were injected tail intravenously into Rag1−/− mice. Livers and lungs were harvested from the mice of different groups at 6 weeks post injection, and tumor metastases determined. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (F) H & E staining on sections from embedded lung and liver tissues showed that high amount of tumor cells infiltrated into lungs and livers obtained from VASH1 shRNA treatment group, but not from the control shRNA treatment group. Tumor metastatic spots were indicated by the arrows.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480723&req=5

Figure 7: Knockdown of VASH1 in human colon cancer HCT116 cells promoted tumor tumorigenesis and metastasis in vivo(A) Knockdown of VASH1 in HCT116 cells dramatically promoted tumor growth in Rag1−/− immunodeficient mice. (B) Representative image of the xenograft tumors shown are obtained from the two groups at the endpoint of the experiments (day 33). (C) The mean weights of xenograft tumors obtained from the two groups at the endpoint of the experiments (day 33). Human colon cancer HCT116 cells (4 × 106/mouse) transfected with VASH1 shRNA or control shRNA, were subcutaneously injected into Rag1−/− mice (n=5). Tumor growth was evaluated (in F). At the end of experiments, tumors were isolated from the sacrificed mice and weighted (G). *p<0.05 compared with the control shRNA group (G). (D) Knockdown of VASH1 in HCT116 cells significantly increased Ki-67+ cell populations compared with control shRNA group in the tumor tissues. Tumor tissue sections were determined for Ki-67 expression using the immunohistochemical staining. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (E) Knockdown of VASH1 in HCT116 cells dramatically increased tumor macrometastatic numbers in lung and liver surfaces. Human colon cancer HCT116 cells (2 × 106/mouse) transfected with VASH1-specific or control shRNA were injected tail intravenously into Rag1−/− mice. Livers and lungs were harvested from the mice of different groups at 6 weeks post injection, and tumor metastases determined. Results shown are mean ± SD from 5 mice per group. **p<0.01 compared with the control shRNA group. (F) H & E staining on sections from embedded lung and liver tissues showed that high amount of tumor cells infiltrated into lungs and livers obtained from VASH1 shRNA treatment group, but not from the control shRNA treatment group. Tumor metastatic spots were indicated by the arrows.
Mentions: We also performed a parallel xenograft model to investigate whether knockdown of VASH1 in colon cancer cells can promote tumor growth and tumorigenesis. Human colon cancer HCT116 cells transfected with VASH1 shRNA or control shRNA, were subcutaneously injected into Rag1−/− mice. As shown in Figure 7A, knockdown of VASH1 in HCT116 cells dramatically promoted tumor growth, compared with the control shRNA–transfected HCT116 cells. In addition, tumor sizes collected from the VASH1 shRNA group on day 33 post inoculation were significantly larger than those in the control shRNA group (Figure 7B). Notably, the average tumor weights obtained from the VASH1 shRNA group also showed much higher than that of control shRNA group (Figure 7C). In addition, knockdown of VASH1 expression in HCT116 cells significantly increased Ki-67+ cell populations in the tumor tissues (Figure 7D). These data indicated that silence of VASH1 expression in tumor cells directly enhanced tumor growth and tumorigenesis in vivo.

Bottom Line: Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients.Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo.In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Jinan Central Hospital, Affiliated to Shandong University, Jinan, P. R. China.

ABSTRACT
Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

No MeSH data available.


Related in: MedlinePlus