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Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation.

Baba Y, Iyama KI, Hirashima K, Nagai Y, Yoshida N, Hayashi N, Miyanari N, Baba H - Br. J. Cancer (2008)

Bottom Line: The positivity was significantly correlated with pTNM stage and poor prognosis.The deactivation of PI3K pathway using the PI3K inhibitor decreased the invasiveness of ESCCs and the secretion of laminin-332 in vitro.Laminin-332 could provide the autocrine positive-feedback loop through PI3K activation, contributing the invasive ability.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, and Department of Surgical Pathology, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan.

ABSTRACT
Laminin-332 is major component of epithelial basement membrane, and has an important role in cell migration and tumour invasion. Recently, the phosphatidylinositol 3-kinase (PI3K) activation induced by laminin-332 during carcinogenesis or tumour invasion has been highlighted in skin squamous cell carcinoma. The expression of laminin-332 in 126 resected oesophageal squamous cell carcinoma (ESCC) specimens was immunohistochemically examined to determine its associations with the clinicopathological characteristics, and the effect of laminin-332 on the invasiveness and the PI3K activation was assessed by in vitro experiments using ESCC cell lines (ESCCs). Sections with immunostaining signals in >30% cancer cells, which were observed in 55 of 126 cases, were judged to be positive for laminin-332. The positivity was significantly correlated with pTNM stage and poor prognosis. Inactivation of the PI3K pathway by laminin-332 blocking antibody suppressed the invasiveness of TE8 cell line, which secreted laminin-332 at high level and had high PI3K activity. The addition of the purified laminin-332 activated the PI3K pathway and increased the invasiveness of TE11 cell line, which secreted laminin-332 at lower level and had low PI3K activity. The deactivation of PI3K pathway using the PI3K inhibitor decreased the invasiveness of ESCCs and the secretion of laminin-332 in vitro. The expression of laminin-332 was one of the prognostic factors of ESCC. Laminin-332 could provide the autocrine positive-feedback loop through PI3K activation, contributing the invasive ability. Therefore, the inhibitor of PI3K pathway might be useful as the anticancer therapies for ESCC.

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Related in: MedlinePlus

(A) The effect of the purified laminin-332 at different concentration on PI3K pathway in TE11 cell line. The addition of the purified laminin-332 activated the PI3K pathway at the concentration of >0.5 μg/ml. (B) The effect of the purified laminin-332 on the invasiveness of TE11 cell line. The number of invaded cells increases with additional laminin-332 (0.5 μg/ml) by comparison with non-treatment or control Albumin (0.5 μg/ml). However, the number of invaded cells decreased with both additional laminin-332 (0.5 μg/ml) and Wortomannin (100 nM).
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fig5: (A) The effect of the purified laminin-332 at different concentration on PI3K pathway in TE11 cell line. The addition of the purified laminin-332 activated the PI3K pathway at the concentration of >0.5 μg/ml. (B) The effect of the purified laminin-332 on the invasiveness of TE11 cell line. The number of invaded cells increases with additional laminin-332 (0.5 μg/ml) by comparison with non-treatment or control Albumin (0.5 μg/ml). However, the number of invaded cells decreased with both additional laminin-332 (0.5 μg/ml) and Wortomannin (100 nM).

Mentions: The effect of the purified laminin-332 on PI3K pathway was examined in vitro using TE11, which secreted laminin-332 at the lowest level. After the incubation with the purified laminin-332 at different concentration for 6 h, the cells were solubilised. The laminin-332 activated the PI3K pathway at the proportion to the concentration of laminin-332 (Figure 5A). The number of invaded cells increased significantly with the purified laminin-332 (0.5 μg ml−1) by comparison with non-treatment or control-purified albumin (0.5 μg ml−1); however the addition of the PI3K inhibitor (Wortmannin;100 nM) decreased the number of invaded cells significantly (Figure 5B).


Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation.

Baba Y, Iyama KI, Hirashima K, Nagai Y, Yoshida N, Hayashi N, Miyanari N, Baba H - Br. J. Cancer (2008)

(A) The effect of the purified laminin-332 at different concentration on PI3K pathway in TE11 cell line. The addition of the purified laminin-332 activated the PI3K pathway at the concentration of >0.5 μg/ml. (B) The effect of the purified laminin-332 on the invasiveness of TE11 cell line. The number of invaded cells increases with additional laminin-332 (0.5 μg/ml) by comparison with non-treatment or control Albumin (0.5 μg/ml). However, the number of invaded cells decreased with both additional laminin-332 (0.5 μg/ml) and Wortomannin (100 nM).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2266844&req=5

fig5: (A) The effect of the purified laminin-332 at different concentration on PI3K pathway in TE11 cell line. The addition of the purified laminin-332 activated the PI3K pathway at the concentration of >0.5 μg/ml. (B) The effect of the purified laminin-332 on the invasiveness of TE11 cell line. The number of invaded cells increases with additional laminin-332 (0.5 μg/ml) by comparison with non-treatment or control Albumin (0.5 μg/ml). However, the number of invaded cells decreased with both additional laminin-332 (0.5 μg/ml) and Wortomannin (100 nM).
Mentions: The effect of the purified laminin-332 on PI3K pathway was examined in vitro using TE11, which secreted laminin-332 at the lowest level. After the incubation with the purified laminin-332 at different concentration for 6 h, the cells were solubilised. The laminin-332 activated the PI3K pathway at the proportion to the concentration of laminin-332 (Figure 5A). The number of invaded cells increased significantly with the purified laminin-332 (0.5 μg ml−1) by comparison with non-treatment or control-purified albumin (0.5 μg ml−1); however the addition of the PI3K inhibitor (Wortmannin;100 nM) decreased the number of invaded cells significantly (Figure 5B).

Bottom Line: The positivity was significantly correlated with pTNM stage and poor prognosis.The deactivation of PI3K pathway using the PI3K inhibitor decreased the invasiveness of ESCCs and the secretion of laminin-332 in vitro.Laminin-332 could provide the autocrine positive-feedback loop through PI3K activation, contributing the invasive ability.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, and Department of Surgical Pathology, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan.

ABSTRACT
Laminin-332 is major component of epithelial basement membrane, and has an important role in cell migration and tumour invasion. Recently, the phosphatidylinositol 3-kinase (PI3K) activation induced by laminin-332 during carcinogenesis or tumour invasion has been highlighted in skin squamous cell carcinoma. The expression of laminin-332 in 126 resected oesophageal squamous cell carcinoma (ESCC) specimens was immunohistochemically examined to determine its associations with the clinicopathological characteristics, and the effect of laminin-332 on the invasiveness and the PI3K activation was assessed by in vitro experiments using ESCC cell lines (ESCCs). Sections with immunostaining signals in >30% cancer cells, which were observed in 55 of 126 cases, were judged to be positive for laminin-332. The positivity was significantly correlated with pTNM stage and poor prognosis. Inactivation of the PI3K pathway by laminin-332 blocking antibody suppressed the invasiveness of TE8 cell line, which secreted laminin-332 at high level and had high PI3K activity. The addition of the purified laminin-332 activated the PI3K pathway and increased the invasiveness of TE11 cell line, which secreted laminin-332 at lower level and had low PI3K activity. The deactivation of PI3K pathway using the PI3K inhibitor decreased the invasiveness of ESCCs and the secretion of laminin-332 in vitro. The expression of laminin-332 was one of the prognostic factors of ESCC. Laminin-332 could provide the autocrine positive-feedback loop through PI3K activation, contributing the invasive ability. Therefore, the inhibitor of PI3K pathway might be useful as the anticancer therapies for ESCC.

Show MeSH
Related in: MedlinePlus