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L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer.

Chen DL, Zeng ZL, Yang J, Ren C, Wang DS, Wu WJ, Xu RH - J Hematol Oncol (2013)

Bottom Line: Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors.Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo.The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong Feng East Load, Guangzhou 510060, China.

ABSTRACT

Background: Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors. The potential role of L1cam in the progression and metastasis of gastric cancer is still not clear and needs exploring.

Methods: Expression of L1cam was evaluated in gastric cancer tissues and cell lines by immunohistochemistry and Western blot. The relationship between L1cam expression and clinicopathological characteristics was analyzed. The effects of L1cam on cell proliferation, migration and invasion were investigated in gastric cancer cell lines both in vitro and in vivo. The impact of L1cam on PI3K/Akt pathway was also evaluated.

Results: L1cam was overexpressed in gastric cancer tissues and cell lines. L1cam expression was correlated with aggressive tumor phenotype and poor overall survival in gastric cancer patients. Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo. The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam. Moreover, the migration and invasion promoted by L1cam overexpression in gastric cancer cells could be abolished by either application of LY294002 (a phosphoinositide-3-kinase inhibitor) or knockdown of endogenous Akt by small interfering RNA.

Conclusions: Our study demonstrated that L1cam, overexpressed in gastric cancer and associated with poor prognosis, plays an important role in the progression and metastasis of gastric cancer.

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L1cam promotes gastric cancer cell growth and metastasis in vivo. (A) SGC7901/Scramble and SGC7901/sh-L1cam cells (1 × 106cells/mouse) were injected subcutaneously into the left and right dorsal flanks of the nude mice (n = 6), tumor volumes were measured on the indicated days. Data points are presented as mean volume ± SD. (B) Histopathology of xenograft tumors, the tumor sections were under HE staining and IHC staining for L1cam and Ki-67. (C) SGC7901/Scramble and SGC7901/sh-L1cam cells (2 × 106cells/mouse) were injected into the tail vein of two groups of nude mice (ten for each group). Six weeks post injection, the mice were killed and the lungs and livers were removed and paraffin embedded.
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Figure 5: L1cam promotes gastric cancer cell growth and metastasis in vivo. (A) SGC7901/Scramble and SGC7901/sh-L1cam cells (1 × 106cells/mouse) were injected subcutaneously into the left and right dorsal flanks of the nude mice (n = 6), tumor volumes were measured on the indicated days. Data points are presented as mean volume ± SD. (B) Histopathology of xenograft tumors, the tumor sections were under HE staining and IHC staining for L1cam and Ki-67. (C) SGC7901/Scramble and SGC7901/sh-L1cam cells (2 × 106cells/mouse) were injected into the tail vein of two groups of nude mice (ten for each group). Six weeks post injection, the mice were killed and the lungs and livers were removed and paraffin embedded.

Mentions: These two cell lines were injected into the left and right flanks of each nude mouse respectively. Tumor size was measured over time; after five weeks, mice were sacrificed and tumors were dissected out. The results showed that tumor growth was significantly inhibited in SGC7901/sh-L1cam cells as compared with that of SGC7901/scramble cells (P < 0.05, Figure 5A). In addition to the difference in tumor volume, we also found tumor tissues formed by injection of SGC7901/scramble cells displayed much stronger staining of L1cam and Ki-67, as detected by immunohistochemical analysis (Figure 5B). To explore the effect of L1cam on in vivo tumor metastasis, the two cell lines were injected into the tail vein of nude mice. Six weeks later, mice were sacrificed and lung and liver metastases were examined. Consistent with the in vitro results, the incidences of metastasis to lung and liver were significantly less in mice injected with SGC7901/sh-L1cam cells than those of SGC7901/scramble cells (P < 0.05, Figure 5C). These data suggest knockdown of L1cam could also inhibit the tumor growth and metastasis of gastric cancer cells in vivo.


L1cam promotes tumor progression and metastasis and is an independent unfavorable prognostic factor in gastric cancer.

Chen DL, Zeng ZL, Yang J, Ren C, Wang DS, Wu WJ, Xu RH - J Hematol Oncol (2013)

L1cam promotes gastric cancer cell growth and metastasis in vivo. (A) SGC7901/Scramble and SGC7901/sh-L1cam cells (1 × 106cells/mouse) were injected subcutaneously into the left and right dorsal flanks of the nude mice (n = 6), tumor volumes were measured on the indicated days. Data points are presented as mean volume ± SD. (B) Histopathology of xenograft tumors, the tumor sections were under HE staining and IHC staining for L1cam and Ki-67. (C) SGC7901/Scramble and SGC7901/sh-L1cam cells (2 × 106cells/mouse) were injected into the tail vein of two groups of nude mice (ten for each group). Six weeks post injection, the mice were killed and the lungs and livers were removed and paraffin embedded.
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Related In: Results  -  Collection

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Figure 5: L1cam promotes gastric cancer cell growth and metastasis in vivo. (A) SGC7901/Scramble and SGC7901/sh-L1cam cells (1 × 106cells/mouse) were injected subcutaneously into the left and right dorsal flanks of the nude mice (n = 6), tumor volumes were measured on the indicated days. Data points are presented as mean volume ± SD. (B) Histopathology of xenograft tumors, the tumor sections were under HE staining and IHC staining for L1cam and Ki-67. (C) SGC7901/Scramble and SGC7901/sh-L1cam cells (2 × 106cells/mouse) were injected into the tail vein of two groups of nude mice (ten for each group). Six weeks post injection, the mice were killed and the lungs and livers were removed and paraffin embedded.
Mentions: These two cell lines were injected into the left and right flanks of each nude mouse respectively. Tumor size was measured over time; after five weeks, mice were sacrificed and tumors were dissected out. The results showed that tumor growth was significantly inhibited in SGC7901/sh-L1cam cells as compared with that of SGC7901/scramble cells (P < 0.05, Figure 5A). In addition to the difference in tumor volume, we also found tumor tissues formed by injection of SGC7901/scramble cells displayed much stronger staining of L1cam and Ki-67, as detected by immunohistochemical analysis (Figure 5B). To explore the effect of L1cam on in vivo tumor metastasis, the two cell lines were injected into the tail vein of nude mice. Six weeks later, mice were sacrificed and lung and liver metastases were examined. Consistent with the in vitro results, the incidences of metastasis to lung and liver were significantly less in mice injected with SGC7901/sh-L1cam cells than those of SGC7901/scramble cells (P < 0.05, Figure 5C). These data suggest knockdown of L1cam could also inhibit the tumor growth and metastasis of gastric cancer cells in vivo.

Bottom Line: Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors.Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo.The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dong Feng East Load, Guangzhou 510060, China.

ABSTRACT

Background: Previous reports have demonstrated that L1cam is aberrantly expressed in various tumors. The potential role of L1cam in the progression and metastasis of gastric cancer is still not clear and needs exploring.

Methods: Expression of L1cam was evaluated in gastric cancer tissues and cell lines by immunohistochemistry and Western blot. The relationship between L1cam expression and clinicopathological characteristics was analyzed. The effects of L1cam on cell proliferation, migration and invasion were investigated in gastric cancer cell lines both in vitro and in vivo. The impact of L1cam on PI3K/Akt pathway was also evaluated.

Results: L1cam was overexpressed in gastric cancer tissues and cell lines. L1cam expression was correlated with aggressive tumor phenotype and poor overall survival in gastric cancer patients. Ectopic expression of L1cam in gastric cell lines significantly promoted cell proliferation, migration and invasion whereas knockdown of L1cam inhibited cell proliferation, migration and invasion in vitro as well as tumorigenesis and metastasis in vivo. The low level of phosphorylated Akt in HGC27 cells was up-regulated after ectopic expression of L1cam, whereas the high level of phosphorylated Akt in SGC7901 cells was suppressed by knockdown of L1cam. Moreover, the migration and invasion promoted by L1cam overexpression in gastric cancer cells could be abolished by either application of LY294002 (a phosphoinositide-3-kinase inhibitor) or knockdown of endogenous Akt by small interfering RNA.

Conclusions: Our study demonstrated that L1cam, overexpressed in gastric cancer and associated with poor prognosis, plays an important role in the progression and metastasis of gastric cancer.

Show MeSH
Related in: MedlinePlus