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Follistatin is a novel biomarker for lung adenocarcinoma in humans.

Chen F, Ren P, Feng Y, Liu H, Sun Y, Liu Z, Ge J, Cui X - PLoS ONE (2014)

Bottom Line: The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value.Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST.In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.

ABSTRACT

Background: Follistatin (FST), a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.

Methods and results: The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.

Conclusions: These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

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The production of FST from lung adenocarcinoma cells.(A) The tumor cells were incubated in 2.5% and 10% FCS-IMEM culture medium, respectively. The non-tumor lung tissue cells were incubated in 10% FCS-IMEM culture medium. The supernatants of cultured cells were harvested at the indicated time point and FST levels were detected by ELISA. ○ Lung adenocarcinoma cells with 10% FCS-IMDM medium. Δ Lung adenocarcinoma cells with 2.5% FCS-IMDM medium. • Non-tumor lung tissue cells with 10% FCS-IMEM medium. (B) FST protein expression in human lung adenocarcinoma cell line A549 cells was examined by immunocytochemical staining with anti-FST antibody (Anti-FST). A procedural background control (Control) was performed using normal mouse IgG instead of anti-FST antibody.
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pone-0111398-g003: The production of FST from lung adenocarcinoma cells.(A) The tumor cells were incubated in 2.5% and 10% FCS-IMEM culture medium, respectively. The non-tumor lung tissue cells were incubated in 10% FCS-IMEM culture medium. The supernatants of cultured cells were harvested at the indicated time point and FST levels were detected by ELISA. ○ Lung adenocarcinoma cells with 10% FCS-IMDM medium. Δ Lung adenocarcinoma cells with 2.5% FCS-IMDM medium. • Non-tumor lung tissue cells with 10% FCS-IMEM medium. (B) FST protein expression in human lung adenocarcinoma cell line A549 cells was examined by immunocytochemical staining with anti-FST antibody (Anti-FST). A procedural background control (Control) was performed using normal mouse IgG instead of anti-FST antibody.

Mentions: To clarify FST production in lung adenocarcinoma, cells obtained from lung adenocarcinoma tissues and non-tumor lung tissues were cultured in vitro and FST levels in the supernatants of cultured cells were detected using ELISA. As shown in Figure 3A, FST production was identified in the supernatant of cultured lung adenocarcinoma cells, but was almost not found in the supernatant of control cells derived from non-tumor lung tissues in 10% FCS-IMDM. Furthermore, the immunocytochemical staining revealed that human lung adenocarcinoma cell line A549 also produced FST protein (Fig. 3B). These data suggested that human lung adenocarcinoma cells secrete FST and the increased FST in serum of patients with lung adenocarcinoma might be produced by lung adenocarcinoma cells.


Follistatin is a novel biomarker for lung adenocarcinoma in humans.

Chen F, Ren P, Feng Y, Liu H, Sun Y, Liu Z, Ge J, Cui X - PLoS ONE (2014)

The production of FST from lung adenocarcinoma cells.(A) The tumor cells were incubated in 2.5% and 10% FCS-IMEM culture medium, respectively. The non-tumor lung tissue cells were incubated in 10% FCS-IMEM culture medium. The supernatants of cultured cells were harvested at the indicated time point and FST levels were detected by ELISA. ○ Lung adenocarcinoma cells with 10% FCS-IMDM medium. Δ Lung adenocarcinoma cells with 2.5% FCS-IMDM medium. • Non-tumor lung tissue cells with 10% FCS-IMEM medium. (B) FST protein expression in human lung adenocarcinoma cell line A549 cells was examined by immunocytochemical staining with anti-FST antibody (Anti-FST). A procedural background control (Control) was performed using normal mouse IgG instead of anti-FST antibody.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4210220&req=5

pone-0111398-g003: The production of FST from lung adenocarcinoma cells.(A) The tumor cells were incubated in 2.5% and 10% FCS-IMEM culture medium, respectively. The non-tumor lung tissue cells were incubated in 10% FCS-IMEM culture medium. The supernatants of cultured cells were harvested at the indicated time point and FST levels were detected by ELISA. ○ Lung adenocarcinoma cells with 10% FCS-IMDM medium. Δ Lung adenocarcinoma cells with 2.5% FCS-IMDM medium. • Non-tumor lung tissue cells with 10% FCS-IMEM medium. (B) FST protein expression in human lung adenocarcinoma cell line A549 cells was examined by immunocytochemical staining with anti-FST antibody (Anti-FST). A procedural background control (Control) was performed using normal mouse IgG instead of anti-FST antibody.
Mentions: To clarify FST production in lung adenocarcinoma, cells obtained from lung adenocarcinoma tissues and non-tumor lung tissues were cultured in vitro and FST levels in the supernatants of cultured cells were detected using ELISA. As shown in Figure 3A, FST production was identified in the supernatant of cultured lung adenocarcinoma cells, but was almost not found in the supernatant of control cells derived from non-tumor lung tissues in 10% FCS-IMDM. Furthermore, the immunocytochemical staining revealed that human lung adenocarcinoma cell line A549 also produced FST protein (Fig. 3B). These data suggested that human lung adenocarcinoma cells secrete FST and the increased FST in serum of patients with lung adenocarcinoma might be produced by lung adenocarcinoma cells.

Bottom Line: The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value.Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST.In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.

ABSTRACT

Background: Follistatin (FST), a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.

Methods and results: The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.

Conclusions: These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

Show MeSH
Related in: MedlinePlus