Adhesion molecules in human pancreatic cancer

BACKGROUND AND OBJECTIVES: Adhesion molecules are cell surface glycoproteins that are important in cell-to-cell and cell-to-extracellular matrix interactions. In the present study, we analyzed the adhesion molecules ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and ELAM-1 (endothelial leukocyte adhesion molecule-1) in human pancreatic cancer. METHODS: ICAM-1, VCAM-1, and ELAM-1 were analyzed in 20 pancreatic cancer specimens and 20 normal pancreatic tissues. mRNA expression encoding ICAM-, VCAM-1, and ELAM-1 was assessed with Northern blot analysis. The distribution and localization of ICAM-1, VCAM-1, and ELAM-1 was determined in the pancreatic specimens by immunohistochemistry. RESULTS: Northern blot analysis revealed a 5.4-fold increase of ICAM-1 (P<0.01) and a 3.7-fold increase in VCAM-1 (P<0.01) mRNA expression in cancer samples in comparison with normal controls. In contrast, ELAM-1 mRNA levels did not show significant differences between the cancer and the normal tissues. Immunohistochemical analysis of cancer tissues showed strong immunostaining for ICAM-1 and VCAM-1, and faint immunostaining for ELAM-1 in the pancreatic cancer cells. Fibrotic or noncancerous pancreatic tissue adjacent to the cancer mass was devoid of any immunoreactivity for ICAM-1, ELAM-1, and VCAM-1. In contrast, the normal pancreas exhibited no immunoreactivity of ICAM-1, ELAM-1, and VCAM-1. CONCLUSIONS: Enhanced expression of ICAM-1 and VCAM-1 in human pancreatic cancers suggests a role in tumor pathogenesis. The increase of these adhesion molecules might influence the detachment of cancer cells in the primary tumor, might contribute to cancer cell migration and the spread of cancer cells to distant organs, or both.     

细胞间粘附分子—1在培养大鼠肝癌细胞的表达

用免疫组织化学方法观察了细胞间粘附分子－１（ＩＣＡＭ－１）在培养大鼠肝癌细胞的定位，为进一步研究肝癌细胞中ＩＡＣＭ－１的意义提供形态学依据。结果表明，几乎所有大鼠肝癌细胞都呈ＩＣＡＭ－１免疫反应性。肝癌细胞中ＩＣＡＭ－１免疫反应物呈细颗粒状，存在于细胞的胞体和突起的胞质中。     

Subcellular localization of intercellular adhesion molecule‐5 (telencephalin) in the visual cortex is not developmentally regulated in the absence of matrix metalloproteinase‐9

The telencephalon‐associated intercellular adhesion molecule‐5 (telencephalin; ICAM‐5) regulates dendritic morphology in the developing brain. In vitro studies have shown that ICAM‐5 is found predominantly within dendrites and immature dendritic protrusions, with reduced expression in mushroom spines, suggesting that ICAM‐5 downregulation is critical for the maturation of synaptic structures. However, developmental expression of ICAM‐5 has not been explored in depth at the ultrastructural level in intact brain tissue. To investigate the ultrastructural localization of ICAM‐5 with transmission electron microscopy, we performed immunoperoxidase histochemistry for ICAM‐5 in mouse visual cortex at postnatal day (P)14, a period of intense synaptogenesis, and at P28, when synapses mature. We observed the expected ICAM‐5 expression in dendritic protrusions and shafts at both P14 and P28. ICAM‐5 expression in these dendritic protrusions decreased in prevalence with developmental age to become localized predominantly to dendritic shafts by P28. To understand better the relationship between ICAM‐5 and the endopeptidase metalloproteinase‐9 (MMP‐9), which mediates ICAM‐5 cleavage following glutamate activation during postnatal development, we also explored ICAM‐5 expression in MMP‐9 null animals. This analysis revealed a similar expression of ICAM‐5 in dendritic elements at P14 and P28; however, an increased prevalence of ICAM‐5 was noted in dendritic protrusions at P28 in the MMP‐9 null animals, indicating that, in the absence of MMP‐9, there is no developmental shift in ICAM‐5 subcellular localization. Our ultrastructural observations shed light on possible functions mediated by ICAM‐5 and their regulation by extracellular proteases. J. Comp. Neurol. 522:676–688, 2013. © 2013 Wiley Periodicals, Inc.     

Intercellular adhesion molecule-1 (ICAM-1) polymorphism is associated with diabetic retinopathy in Type 2 diabetes mellitus.

AIMS: Leucocyte adhesion to the diabetic retinal vasculature has been implicated in the pathogenesis of diabetic retinopathy. We evaluated the relationship between genetic polymorphisms in leucocyte and endothelial cell adhesion molecules and diabetic retinopathy in Type 2 diabetes mellitus. METHODS: We determined ICAM-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), and leucocyte endothelial adhesion molecule-1 (LECAM-1) genotypes in 81 patients with and 50 without diabetic retinopathy. RESULTS: The frequency of ICAM-1 469KK genotype and K allele were significantly higher in the patients with diabetic retinopathy than in those without retinopathy (genotype 42% vs. 20%, chi2 = 6.70, P = 0.035; allele 66% vs. 50%, chi2 = 6.49, P = 0.011). With regard to the PECAM-1 V125L and LECAM-1 P213S polymorphisms, there were no significant associations between the distribution of genotypes or allele frequencies and the presence of diabetic retinopathy. Independent of other risk factors, the ICAM-1 469KK genotype was associated with a 3.51-fold increased risk for retinopathy. CONCLUSIONS: These data suggest that the ICAM-1 469KK genotype could be a genetic risk factor for retinopathy in Type 2 diabetes mellitus.     

人直肠腺癌淋巴管内皮细胞ICAM-1的转录调节

为探讨癌细胞淋巴管侵润转移机理，对8例直肠腺癌患者的癌周组织和转移淋巴结，以及5例正常人的直肠组织和淋巴结，采用免疫组织化学方法，检测细胞间细胞粘附分子（ICAM－1）和核转录因子KBp65（NFKBp65）的表达。同时通过地高辛碱性磷酸酶标记的寡核苷酸探针，利用原位杂交技术，对8例直肠腺癌患者的癌周组织和转移淋巴结以及5例正常人的直肠组织和淋巴结，进行ICAM－1基因的NFKB结合位点的检测。结果显示：直肠腺癌病人转移的淋巴结和癌周直肠组织中的淋巴管内皮细胞都有ICAM－1和NFKBp65表达，而在正常人的淋巴管内皮细胞无ICAM－1和NFKBp65的表达；直肠腺癌病人转移淋巴结和癌周直肠组织中的淋巴管内皮细胞核内ICAM１的启动子中存在有NFKB 结合位点。提示ICAM－1的转录，取决于可诱导的NFKB 蛋白质复合物与ICAM－1的NFKB部位结合，阻碍NFKB因子的活化能够防止癌细胞的淋巴管转移。