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

• Published in: British journal of cancer 2008-03, Vol.98 (5), p.974-980
• Main Authors: Baba, Y, Iyama, K-i, Hirashima, K, Nagai, Y, Yoshida, N, Hayashi, N, Miyanari, N, Baba, H
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - chemistry; Carcinoma, Squamous Cell - pathology; Cell adhesion & migration; Cell Adhesion Molecules - analysis; Cell Adhesion Molecules - physiology; Cell Line, Tumor; Drug Resistance; Epidemiology; ErbB Receptors - analysis; Esophageal cancer; Esophageal Neoplasms - chemistry; Esophageal Neoplasms - pathology; Humans; Immunohistochemistry; Integrin beta4 - analysis; Kalinin; Kinases; Lymphatic system; Medical prognosis; Medical research; Metastasis; Molecular Diagnostics; Molecular Medicine; Neoplasm Invasiveness; Oncology; Patients; Phosphatidylinositol 3-Kinases - physiology; Yeast
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604252

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.