Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation.
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.
Baba
Y
Y
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.
Iyama
K-I
KI
Hirashima
K
K
Nagai
Y
Y
Yoshida
N
N
Hayashi
N
N
Miyanari
N
N
Baba
H
H
D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000032:analysis; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D039663:Integrin beta4 / Q000032:analysis; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D066246:ErbB Receptors; D039663:Integrin beta4; D019869:Phosphatidylinositol 3-Kinases; D000097794:Kalinin