The Effect Of Hypoxia On The Expression Of Celluar Adhesion Molecules And Invasion In Pancreatic Carcinoma

【Objective】To investigate the regulation of HIF-1α,E-cadherin,Integrinα₅,Integrinβ₁ and the increasing invasion of pancreatic carcinoma under hypoxia, the expression of HIF-1α,E-cadherin,Integrinα₅ and Integrinβ₁ was detected in pancreatic carcinoma tissues and pancreatic carcinoma cell line PANC-1 as well as the tumor cell invasive capacity was examined in hypoxia condition.【Methods】Immunohistochemistry was used to detect the expression of HIF-1αand its correlation with E-cadherin and Integrinα₅β₁ in 34 pancreatic carcinoma samples. Its relationship with the pathological characteristics of tumor was analyzed. Then the expression of HIF-1α,E-cadherin and Integrinα₅β₁ was examined by using Western blot and RT-PCR in PANC-1 cells under hypoxia culture with or without YC-1 in vitro. The invasiveness of pancreatic cancer cell under hypoxia was measured by matrigel assay. Their interrelations and relationship with the tumor invasion were analyzed.【results】1 The expression of HIF-1αand celluar adhesion molecules in pancreatic carcinoma tissues and its clinical signifcanceIn pancreatic carcinoma, the positive expression rates of HIF-1α,E-cadherin,Integrinα₅ and Integrinβ₁ were 76.47%,38.21%,47.06%and 91.18% respectively,which were significant different to theirs in normal tissues (p <0.05). The expression of HIF-1αprotein was negative correlation with E-cadherin and Integrinα₅ (r=-0.476,p <0.01;r=-0.362,p <0.05), was positive correlation with integrinβ₁ (r=0.343,p <0.05). The expression of HIF-1αprotein was significantly correlated with tumor sizes, pathological stages and lymph node metastasis(p <0.05). The expressions of E-cadherin,integrinα5 and integrinβ1 protein were significantly correlated with pathological stages and lymph node metastasis(p <0.05).2 The effect of hopoxia on the expressions of HIF-1α,celluar adhesion molecules and invasiveness in PANC-1 cellThe expression of HIF-1αand integrinβ₁ mRNA was not significantly changed, when the PANC-1 cell was exposed to varies hypoxia time with or without YC-1. The expression of E-cadherin and integrinα₅ mRNA was significantly reduced in hypoxia condition and declined with the prolong time of hypoxia (P <0.05).YC-1 could maintain the level of mRNA expression of them in hypoxia similar with normoxia(P <0.05). The expression of HIF-1αprotein increased when cells were exposed to hypoxia (P <0.05) and reached peak at hypoxia 24 hours. The expression markedly decreased by using YC-1(P <0.05), was similar with normoxia culture. The expression of E-cadherin and integrinα₅ protein reduced significantly after hypoxia and declined with the prolong time of hypoxia (P <0.05). The expression was increased by YC-1 treatment(P <0.05). The expression of HIF-1αprotein was negative correlation with E-cadherin and integrinα₅ (r=-0.954,p <0.05;r=-0.951,p <0.05). The expression of integrinβ₁ protein was not significantly changed when exposed to hypoxia with or without YC-1. Invasion assay showed that the invasive capacity of the PANC-1 cells was signifcantly facilitated under hypoxia compared with that of mormoxia(P <0.05). This effect was inhibited by using YC-1(P <0.05).【Conclusions】1 In human pancreatic carcinoma, the expression of HIF-1αand integrinβ₁ are strong, but the expression of E-cadherin and integrinα₅ is reduced. The expression of HIF-1αprotein is significantly correlated with tumor sizes, pathological stages and lymph node metastasis. The expressions of E-cadherin,Integrinα₅ and Integrinβ₁ protein are significantly correlated with pathological stages and lymph node metastasis. It is suggested that HIF-1α,E-cadherin,Integrinα₅ and Integrinβ₁ play an important role in progression of pancreatic carcinoma.2 Hypoxia induces up-regulation of HIF-1αand down-regulation of E-cadherin and integrinα₅. These effects are inhibited by YC-1. It is suggests HIF-1αmay be an important factor on down-regulating the expressions of E-cadherin and integrinα₅ by hypoxia.3 Hypoxia increases the invasiveness of PANC-1 cells. YC-1 inhibits the hypoxia-increased invasive capacity. Hypoxia induces down-regulation of E-cadherin and integrinα₅ via HIF-1αpathway, decreases cell adhesion and accelerates the invasion of pancreatic carcinoma.