Sawai Hirozumi, Funahashi Hitoshi, Yamamoto Minoru, Okada Yuji, Hayakawa Tetsushi, Tanaka Moritsugu, Takeyama Hiromitsu, Manabe Tadao
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Oncology. 2003;65(2):167-73. doi: 10.1159/000072343.
To investigate the mechanisms of metastasis formation in metastatic human pancreatic cancer, we examined the enhancement in integrin expression, and adherence to and invasiveness into extracellular matrix (ECM) proteins of human pancreatic cancer cells after exposure to interleukin (IL)-1alpha.
Expression of IL-1 receptor type I (IL-1RI) and alterations in integrin subunits by IL-1alpha were examined by flow-cytometric analysis and by cellular enzyme-linked immunosorbent assay in four human pancreatic cancer cell lines (BxPC-3, PaCa-2, PANC-1, and SW1990), respectively. In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the adhesive and invasive interaction between cancer cells and the putative integrin ECM ligands. Furthermore, immunohistochemistry was used to assess integrins and IL-1R1 expression in pancreatic tissues.
In metastatic cancer cells, expression of the alpha(6) subunit was enhanced by IL-1alpha treatment. While metastatic cancer cells exhibited preferential adherence to and invasion into laminin, these properties were enhanced by IL-1alpha. The alpha(6) subunit and IL-1RI were strongly expressed in pancreatic tissues from pancreatic cancer patients with liver metastasis.
In pancreatic cancer, IL-1alpha enhanced alpha(6)beta(1)-integrin expression, probably via increased IL-1RI levels. Our results indicated that alpha(6)beta(1)-integrin and IL-1RI expression may play important roles in metastasis formation.
为了研究人转移性胰腺癌转移形成的机制，我们检测了白细胞介素（IL）-1α作用后人胰腺癌细胞整合素表达的增强情况，以及其对细胞外基质（ECM）蛋白的黏附及侵袭能力。
分别采用流式细胞术分析和细胞酶联免疫吸附测定法，检测了四种人胰腺癌细胞系（BxPC-3、PaCa-2、PANC-1和SW1990）中I型IL-1受体（IL-1RI）的表达以及IL-1α对整合素亚基的影响。此外，还进行了癌细胞对ECM蛋白的黏附及侵袭试验，以研究整合素表达增加是否会影响癌细胞与假定的整合素ECM配体之间的黏附及侵袭相互作用。此外，采用免疫组织化学方法评估胰腺组织中整合素和IL-1R1的表达。
在转移性癌细胞中，IL-1α处理可增强α(6)亚基的表达。虽然转移性癌细胞对层粘连蛋白表现出优先黏附及侵袭能力，但IL-1α可增强这些特性。α(6)亚基和IL-1RI在伴有肝转移的胰腺癌患者的胰腺组织中强烈表达。
在胰腺癌中，IL-1α可能通过增加IL-1RI水平来增强α(6)β(1)-整合素的表达。我们的结果表明，α(6)β(1)-整合素和IL-1RI的表达可能在转移形成中起重要作用。
