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

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.

• Authors: Y Baba, K-I Iyama, K Hirashima, Y Nagai, N Yoshida, N Hayashi, N Miyanari, H Baba
• Journal: British journal of cancer (Br J Cancer) Vol. 98 Issue 5 Pg. 974-80 (Mar 11 2008) ISSN: 0007-0920 [Print] England
• PMID: 18283320 (Publication Type: Journal Article)

Chemical References

• Cell Adhesion Molecules
• Integrin beta4
• Phosphatidylinositol 3-Kinases
• ErbB Receptors

Topics

• Carcinoma, Squamous Cell (chemistry, pathology)
• Cell Adhesion Molecules (analysis, physiology)
• Cell Line, Tumor
• ErbB Receptors (analysis)
• Esophageal Neoplasms (chemistry, pathology)
• Humans
• Immunohistochemistry
• Integrin beta4 (analysis)
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (physiology)
• Kalinin