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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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The prognostic significance of L1cam in gastric cancer patients. (A) Representative photos of L1cam expression in 156 gastric cancer patients, a, negative staining of L1cam in adjacent normal tissues; b, weak staining of L1cam in well differentiated gastric cancer tissues; c, moderate staining of L1cam in cancer tissues; d, strong staining of L1cam in cancer tissues, amplification (×100). (B) Kaplan-Meier analysis of overall survival based on L1cam expression in all 156 patients. (C) and (D) Kaplan-Meier analysis of overall survival based on L1cam expression in stage I-II (C) and stage III-IV gastric cancer patients (D).
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Figure 2: The prognostic significance of L1cam in gastric cancer patients. (A) Representative photos of L1cam expression in 156 gastric cancer patients, a, negative staining of L1cam in adjacent normal tissues; b, weak staining of L1cam in well differentiated gastric cancer tissues; c, moderate staining of L1cam in cancer tissues; d, strong staining of L1cam in cancer tissues, amplification (×100). (B) Kaplan-Meier analysis of overall survival based on L1cam expression in all 156 patients. (C) and (D) Kaplan-Meier analysis of overall survival based on L1cam expression in stage I-II (C) and stage III-IV gastric cancer patients (D).

Mentions: To evaluate the clinicopathological significance of L1cam in gastric cancer, immunohistochemistry analysis was performed in 156 gastric cancer samples. As shown in Figure 2A, L1cam protein was mainly located in the cytoplasm and cell membrane of tumor cells. Positive staining was observed in 114 of 156 (73%) cases. The patients were divided into the L1cam low expression group (n = 85) and the L1cam high expression group (n = 71) based on IHC scores. The correlation between L1cam expression and clinicopathological characteristics was listed in Table 1. High expression of L1cam was positively associated with large tumor size (P = 0.001), lymph node invasion (P = 0.007), peritoneal dissemination (P = 0.019), liver metastasis (P = 0.013) and TNM stage (P = 0.002). Kaplan-Meier analysis with log-rank test was performed to assess the prognostic significance of L1cam in gastric cancer. A significant difference of overall survival was found between patients with high L1cam expression and patients with low L1cam expression. Kaplan-Meier survival curves showed high L1cam expression was associated with poor overall survival (P < 0.001, Figure 2B-D, Table 1). Univariate analysis demonstrated patients with high L1cam expression tended to have a higher risk of death (HR = 2.73, 95% CI, 1.76-4.25; P < 0.001, Table 2). In addition, other parameters including tumor size, lymph node invasion and TNM stage were proved to be associated with overall survival as indicated by univariate analysis (Table 2). However, age, gender, differentiation status and therapeutic strategy had no prognostic significance in this studied population (Table 2, Additional file1: Figure S1). Multivariate analysis showed only L1cam expression was an independent prognostic factors for gastric cancer patients (P = 0.022, Table 2).


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)

The prognostic significance of L1cam in gastric cancer patients. (A) Representative photos of L1cam expression in 156 gastric cancer patients, a, negative staining of L1cam in adjacent normal tissues; b, weak staining of L1cam in well differentiated gastric cancer tissues; c, moderate staining of L1cam in cancer tissues; d, strong staining of L1cam in cancer tissues, amplification (×100). (B) Kaplan-Meier analysis of overall survival based on L1cam expression in all 156 patients. (C) and (D) Kaplan-Meier analysis of overall survival based on L1cam expression in stage I-II (C) and stage III-IV gastric cancer patients (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3717076&req=5

Figure 2: The prognostic significance of L1cam in gastric cancer patients. (A) Representative photos of L1cam expression in 156 gastric cancer patients, a, negative staining of L1cam in adjacent normal tissues; b, weak staining of L1cam in well differentiated gastric cancer tissues; c, moderate staining of L1cam in cancer tissues; d, strong staining of L1cam in cancer tissues, amplification (×100). (B) Kaplan-Meier analysis of overall survival based on L1cam expression in all 156 patients. (C) and (D) Kaplan-Meier analysis of overall survival based on L1cam expression in stage I-II (C) and stage III-IV gastric cancer patients (D).
Mentions: To evaluate the clinicopathological significance of L1cam in gastric cancer, immunohistochemistry analysis was performed in 156 gastric cancer samples. As shown in Figure 2A, L1cam protein was mainly located in the cytoplasm and cell membrane of tumor cells. Positive staining was observed in 114 of 156 (73%) cases. The patients were divided into the L1cam low expression group (n = 85) and the L1cam high expression group (n = 71) based on IHC scores. The correlation between L1cam expression and clinicopathological characteristics was listed in Table 1. High expression of L1cam was positively associated with large tumor size (P = 0.001), lymph node invasion (P = 0.007), peritoneal dissemination (P = 0.019), liver metastasis (P = 0.013) and TNM stage (P = 0.002). Kaplan-Meier analysis with log-rank test was performed to assess the prognostic significance of L1cam in gastric cancer. A significant difference of overall survival was found between patients with high L1cam expression and patients with low L1cam expression. Kaplan-Meier survival curves showed high L1cam expression was associated with poor overall survival (P < 0.001, Figure 2B-D, Table 1). Univariate analysis demonstrated patients with high L1cam expression tended to have a higher risk of death (HR = 2.73, 95% CI, 1.76-4.25; P < 0.001, Table 2). In addition, other parameters including tumor size, lymph node invasion and TNM stage were proved to be associated with overall survival as indicated by univariate analysis (Table 2). However, age, gender, differentiation status and therapeutic strategy had no prognostic significance in this studied population (Table 2, Additional file1: Figure S1). Multivariate analysis showed only L1cam expression was an independent prognostic factors for gastric cancer patients (P = 0.022, Table 2).

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