Inhibition of cellular adhesion in human umbilical vein endothelial cells by NF-kappaB inhibitor DHMEQ under flow

We previously designed and synthesized DHMEQ as an inhibitor of NF-kappaB. In the present study, we looked into the effect of DHMEQ on the cell adhesion in human umbilical vein endothelial cells (HUVEC) under flow. We used freshly prepared HUVEC and human mononuclear cells throughout the experiment. DHMEQ inhibited TNF-alpha-, IL-1beta-, and LPS-induced NF-kappaB activation in HUVEC. It also inhibited TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. DHMEQ also inhibited TNF-alpha-induced mononuclear cell-HUVEC adhesion. The effect of DHMEQ was more prominent when the cells were under shear stress. DHMEQ inhibited the adhesion between HUVEC and HT-29 colon cancer cells more clearly under the flow condition than under the static condition of the culture medium. These results suggest that DHMEQ, being a unique inhibitor of NF-kappaB, may be effective in suppressing atherosclerosis and metastasis by inhibiting the expression of adhesion molecules.     

Differential endothelial CAM-expression after stimulation with supernatants of LPS- and cytokine-stimulated HT-29 and ST-ML-12 tumor cells growing as monolayer cultures and multicellular spheroids

The mechanisms of tumor metastasis in vitro have been principally investigated using monolayer culture systems. In vivo, however, multicellular clusters of tumor cells rather than individual cells appear to penetrate the microvasculature. Thus, the multicellular tumor spheroid model represents a more suitable tool to study tumor cell-endothelial interactions. Our interest has centered on the role of inflammation on tumor intra- and extravasation. The expression of three endothelial cell adhesion molecules (CAM), ICAM-1, VCAM-1 and E-selectin, on HUVEC after incubation with supernatants of previously LPS-, TNF-alpha- or IL-1 beta-stimulated HT-29 (colon adenocarcinoma) and ST-ML-12 (melanoma) tumor cells growing as monolayers and spheroids, was compared using cell enzyme immunoassay. The results indicated that important differences in the expression of CAM between monolayers and spheroids exist depending on the tumor cell line. The possible significance of LPS for colon carcinomas was underlined by the spheroid-model results. With respect to the influence of intestinal bacteria on the behaviour of colon carcinomas, the spheroid model could be a useful in vitro system for a more realistic simulation of in vivo conditions.     

Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium

In this experimental study, the influence of surgery-induced proinflammatory cytokines on tumor recurrence in the lung was investigated. A reproducible human in vitro assay was developed to study the adhesion of HT29 colon carcinoma cells to monolayers of microvascular endothelial cells of the lung (HMVECs-L) or human umbilical venous endothelial cells (HUVECs). Preincubation of HMVECs-L with maximally active concentrations of IL-1beta and TNF-alpha, but not with IL-6, resulted in at least 250% adhesion compared to control adhesion (p 相似文献   

Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery

The serum concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 63 patients with colorectal cancer and in 51 controls by an enzyme-linked immunosorbent assay (ELISA). Their relationship to clinicopathological variables and patient survival and changes in their levels after surgery were examined. Colorectal cancer patients showed significantly higher serum levels of E-selectin, ICAM-1 and VCAM-1 compared with healthy controls. There was a significant association between the serum levels of these molecules, disease stage and the presence of both lymph node and distant metastases. Both ICAM-1 and VCAM-1 levels correlated with serum E-selectin and carcinoembryonic antigen (CEA) levels. Serum levels of all three molecules decreased significantly after radical resection of the tumour. Elevated pre-operative E-selectin, ICAM-1 and VCAM-1 levels were significant prognostic factors, although not independent of stage, for patient survival. These findings suggest that serum concentrations of E-selectin, ICAM-1 and VCAM-1 may reflect tumour progression and metastasis. Since these markers are linked to CEA levels, it is uncertain whether their measurement will prove cost-effective in colorectal cancer management.     

Tumor-Endothelium Cross Talk Blocks Recruitment of Neutrophils to Endothelial Cells: A Novel Mechanism of Endothelial Cell Anergy

Tumor cells have evolved effective strategies to escape the host immune response. The objective of this study was to determine whether tumor cells can condition endothelial cells in a specific manner to prevent subsequent adhesion of polymorphonuclear neutrophils (PMNs) and/or peripheral blood lymphocytes (PBLs). Human umbilical vein endothelial cells (HUVECs) and UKF-NB-4 neuroblastoma tumor cells were established in coculture on opposite sides of porous transwell filters. After 24 hours with and without HUVEC conditioning, PMNs or PBLs were added to the HUVEC monolayer. Adhesion to conditioned HUVEC versus adhesion to nonconditioned HUVEC was compared. Effects on endothelial CD44v4, CD44v5, CD44v7, intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1) adhesion receptor expression were analyzed by flow cytometry, intracellular signaling proteins of the mitogen-activated protein kinase pathway and protein kinase C (PKC) subtypes quantified by Western blot analysis. Endothelial conditioning led to a distinct reduction in PMN but not in PBL adhesion to HUVEC. CD44 was significantly reduced, whereas ICAM-1, E-selectin, and VCAM-1 were not altered during HUVEC conditioning. Antibody blockade against CD44v4, CD44v5, and CD44v7 inhibited PMN but not PBL binding. The observed effects were caused by direct tumor cell-HUVEC contact because addition of isolated tumor cell membrane fragments but not of soluble cell culture supernatant to HUVEC induced the CD44 receptor loss. PKCα activity was strongly enhanced in conditioned HUVEC. Blocking PKC prevented the reduction in PMN binding, indicating that this protein is involved in PMN adhesion regulation. A novel tumor escape strategy is presented here. Cell contact-dependent adhesion of tumor cells to the vascular wall promotes down-regulation of endothelial CD44 receptor expression, impairing an effective neutrophil attack.     

Egfl7 promotes tumor escape from immunity by repressing endothelial cell activation

Downregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines [IFN-γ, interleukin-12 (IL-12)] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-γ. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control.     

Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in urological malignancies

Several studies suggest that cellular adhesion molecules (CAM) play a role in cancer progression and metastasis. To evaluate the role of these molecules as possible tumor markers in patients with urological malignancies, we examined the serum levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cellcular adhesion molecule-1 (VCAM-1) and E-selectin in patients with renal cell-, bladder-, prostate- and testicular cancer. Serum levels of 237 patients with urological cancers, renal cell carcinoma (n = 47), bladder cancer (n = 81), prostate cancer (n = 87) and testicular cancer (n = 22) and a group of 41 patients with benign prostate hyperplasia (BPH) as well as a 42 healthy control persons were examined for CAMs by specific ELISA tests. Serum CAM concentrations of all tumor patients were compared with controls and within the group according to T stage, N stage, tumor grade and extent of distant metastasis. Our results demonstrate that ICAM-1 and VCAM-1 serum levels are not stage dependently elevated; in contrary, they demonstrate a wide range and are highly variable throughout the different cancer types. In renal cell cancer and in bladder cancer, there is a significant difference for ICAM-1 between controls and T3 and T4 and metastatic cancers. A similar difference was found for VCAM-1, however not for E-selectin in any tumor group. Testicular cancer and prostate cancer did not demonstrate any difference in CAM serum levels between patients with tumors and controls. In metastatic renal cell-, bladder- and prostate cancer, the serum levels of ICAM-1 and VCAM-1 showed a tendency to correlate with the extent of metastatis although no statistical difference between patients with a single metastatic lesion and patients with multiple lesions could be demonstrated. The results of this study implicate a rather limited role of cellular adhesion molecules. Despite of significant ICAM-1 or VCAM-1 serum levels in some locally advanced tumors or metastatic disease, this observation does not provide enough relevant clinical information for use as tumor markers.     

Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules

The role of cell adhesion molecules has been studied extensively in the process of inflammation, and these molecules are critical components of carcinogenesis and cancer metastasis. This study investigated the effect of tanshinone I derived from the traditional herbal medicine, Salvia miltiorrhiza Bunge, on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. Furthermore, this study investigated the effect of tanshinone I on cancer growth, invasion and angiogenesis on human breast cancer cells MDA-MB-231, both in vitro and in vivo. Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h. Pretreatment with tanshinone I significantly reduced adhesion of either monocyte U937 or MDA-MB-231 cells to HUVECs. Interestingly, the inhibitory effect of tanshinone I on monocyte and cancer cell adhesion to HUVECs was mimicked by transfection with ICAM-1 and VCAM-1 small interfering RNA. In addition, tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix. Additionally, reduction of tumor mass volume and decrease of metastasis incidents by tanshinone I were observed in vivo. In conclusion, this study provides a potential mechanism for the anticancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.     

Mutation and functional analysis of IL-13 receptors in human malignant glioma cells

We have previously demonstrated that human brain tumor cells, in particular glioblastoma multiforme (GBM), express abundant receptors for interleukin-13 on the cell surface. These receptors are composed of IL-13 receptor (IL-13R)alpha1, IL-13Ralpha2, and IL-4Ralpha chains. The significance of overexpression of IL-13R on tumor cells is not known. Because expression of IL-13R on glioma cells is an unexpected phenomenon, we examined whether these receptors are polymorphic. Therefore, we analyzed cDNA for IL-13Ralpha1 and IL-13Ralpha2 chain genes by PCR-based single-strand conformation polymorphism and direct sequencing techniques for a possible polymorphism in 19 GBM, one normal human astrocyte, and two fibroblast cell lines. All analyzed samples except normal astrocytes overexpressed IL-13Ralpha2; however, none of these cell lines showed a mutation in cDNA for IL-13Ralpha2 chain. In contrast, all GBM samples, normal astrocytes, and fibroblasts expressed mRNA for IL-13Ralpha1 with apparent single nucleotide polymorphism in the transmembrane domain. To study the function of IL-13R on brain tumor cells, we investigated the regulation of adhesion molecules by IL-13 as assessed by flow cytometric analysis. A172 cell line expressed a low level of vascular cell adhesion molecule-1 (VCAM-1), while U251 and LA1-5g cell lines expressed intercellular adhesion molecule-1 (ICAM-1). On the other hand E-selectin was not expressed in any cell lines. Interestingly, IL-13 increased the expression level of VCAM-1 in A172 cell line in a dose- and time-dependent manner. However, IL-13 did not modulate any other adhesion molecules. These results suggest that IL-13R on GBM cells are not rearranged but appear to be functional.     

A pentacyclic triterpene natural product,ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis

Here we showed that ursolic acid (UA), a pentacyclic triterpene natural product, and its novel prodrug derivative US597 suppressed cancer cells adhesion, invasion and migration. This effect was accompanied by inhibition of focal adhesion signaling pathway including alterations in ICAM-1, VCAM-1, E-selectin, P-selectin, integrin α6β1, FAK, Src, paxillin and PTEN. While oral administration of UA or US597 increases survival rate of melanoma lung metastasis in C57BL/6 mice, US597 treatment extend the survival rate above that of UA. Immunohistochemical analysis revealed that US597 treatment regulates ICAM-1, a biomarker of metastasis. We did not detect side effects with US597 in mice such as weight loss, viscera tissues toxicity and blood cell abnormalities. Thus, UA and US597 are potential drug candidates for preventing cancer metastasis. Molecular and cellular study data suggest that UA and US597 modulate expression of cell adhesion molecules within focal adhesion signaling pathway leading to cancer cell motility.     

Simvastatin reduces tumor cell adhesion to human peritoneal mesothelial cells by decreased expression of VCAM-1 and β1 integrin

Peritoneal carcinomatosis describes cancer metastasis onto the surface of the peritoneum. It is frequently caused by ovarian and colorectal cancer. Once a tumor has penetrated the peritoneum, cancer cells disseminate into the abdominal cavity. Additionally, surgery can account for the spread of free tumor cells. Their subsequent adhesion to mesothelial cells (HMCs) initiates peritoneal carcinomatosis. Therefore, this study analyzed the effect of simvastatin on tumor cell adherence. HMCs were isolated from human greater omentum. Fluorescence-labeled tumor cells (SKOV-3, OvCar-29, OAW42, FraWü; ovarian/HT29; colorectal) were incubated on confluent mesothelial monolayers with 10 μM simvastatin for 48 h. Adhesion was quantified using a fluorescence reader. Expression of the adhesion molecules VCAM-1, ICAM-1 and β1 integrin chain under the influence of simvastatin 0.1-100 μM for 24-72?h was analyzed using flow cytometry. Simvastatin significantly reduced the adhesion of all ovarian cancer cells and HT29 to HMCs (P≤0.001). Concomitantly simvastatin decreased the expression of VCAM-1 on HMCs. ICAM-1 and β1 integrin chain expression on ovarian cancer cells was also clearly reduced. By contrast, the expression of the analyzed adhesion molecules on HT29 cells remained unchanged. Simvastatin clearly inhibits tumor cell adhesion to HMCs. In the case of ovarian cancer cell lines it appears to be mediated by decreased expression of both VCAM-1 on HMCs and the integrin α4β1 on tumor cells. As an example of adhesion molecule down-regulating drugs, simvastatin may provide a novel therapeutic approach to the prevention of peritoneal carcinomatosis.     

The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications

In this study we demonstrate that tumor necrosis factor alpha (TNFalpha) triggers only modest proliferation, as well as p44/p42 mitogen-activated protein kinase (MAPK) and NF-kappaB activation, in MM.1S multiple myeloma (MM) cells. TNFalpha also activates NF-kappaB and markedly upregulates (fivefold) secretion of interleukin-6 (IL-6), a myeloma growth and survival factor, in bone marrow stromal cells (BMSCs). TNFalpha in both a dose and time dependent fashion induced expression of CD11a (LFA-1), CD54 (intercellular adhesion molecule-1, ICAM-1), CD106 (vascular cell adhesion molecule-1, VCAM-1), CD49d (very late activating antigen-4, VLA-4), and/or MUC-1 on MM cell lines; as well as CD106 (VCAM-1) and CD54 (ICAM-1) expression on BMSCs. This resulted in increased (2-4-fold) per cent specific binding of MM cells to BMSCs, with related IL-6 secretion. Importantly, the proteasome inhibitor PS-341 abrogated TNFalpha-induced NF-kappaB activation, induction of ICAM-1 or VCAM-1, and increased adhesion of MM cells to BMSCs. Agents which act to inhibit TNFalpha may therefore abrogate the paracrine growth and survival advantage conferred by MM cell adhesion in the BM microenvironment.     

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.     

Importance of E-selectin (ELAM-1) and sialyl lewisa in the adhesion of pancreatic carcinoma cells to acttvated endothelium

Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewis^a (SLe^a) and sialyl Lewis^x (SLe^x). Activation of HUVEC with interleukin l-β (IL-Iβ) or tumor necrosis factor-α (TNF-α), but not with interferon-γ (IFN-γ), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-I β and/or TNF-α. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-I) on HUVEC, and was evident at both 25°C and 4°C. Anti-E-selectin and anti-SLe^a blocked the augmented attachment, whereas anti-SLe^x, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 β and TNF-α, and is mediated by SLe^a on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.     

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.     

E-选择素介导肝癌细胞HepG2和内皮细胞的早期黏附

目的　探讨sLeX 和E 选择素在肝癌细胞与内皮细胞早期黏附中的作用 ,并筛选有临床应用前景的抗黏附药物。方法　应用荧光活细胞染料BCECF -AM标记HepG2肝癌细胞。应用体外黏附实验检测肝癌细胞HepG2和人脐静脉内皮细胞 (HUVEC)的黏附 ,并测试不同药物对二者黏附的影响。结果　sLeX 和E 选择素是肝癌细胞与内皮细胞早期黏附的必要条件之一。HepG2条件培养液处理HUVEC可促进其与HepG2的黏附 ;地塞米松、氧化苯砷、左旋咪唑、放线菌素和sLeX 的类似物在低浓度下即有明显的抗黏附作用。结论　肝癌细胞可能分泌炎症因子样物质 ,促进靶组织内皮细胞的活化 ,地塞米松、氧化苯砷、左旋咪唑、放线菌素和sLeX 的类似物可能成为较有前景的、预防肝癌转移的抗黏附药物     

Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in human malignancies.

Cellular adhesion molecules have been implicated in tumour progression and metastasis. This study examines for the first time the serum concentrations of circulating VCAM-1 and E-selectin in a consecutive series of 110 cancer patients seen in a general medical oncology clinic, and confirms and extends previous studies reporting measurement of circulating ICAM-1. Soluble ICAM-1 and VCAM-1 levels were significantly higher in all the patient groups compared with the controls whereas soluble E-selectin was significantly higher in the ovarian, breast and GI cancer groups and lower in the myeloma group. The significance of these results together with the possible sources and stimuli for release of these adhesion molecules are discussed.     

Lipopolysaccharide induces the interactions of breast cancer and endothelial cells via activated monocytes

The adhesion of circulating cancer cells to vascular endothelium is a key step in hematogenous metastasis. Cancer cell-endothelium interactions are mediated by cell adhesion molecules that can also be involved in the arrest of monocytes and other circulating leukocytes on endothelium in inflammation. Static and microfluidic flow adhesion assays as well as flow cytometry were conducted in this study to elucidate the role of monocytes, bacterial lipopolysaccharide (LPS), and histamine in breast cancer cell adhesion to vascular endothelial cells. Tumor necrosis factor-α (TNF-α) released from LPS-treated monocytes triggered the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Histamine augmented the TNF-α effect, leading to a high number of arrested breast cancer cells under both static and shear flow conditions. LPS-treated monocytes were shown to enhance the arrest of breast cancer cells by anchoring the cancer cells to activated endothelial cells. This anchorage was achieved by binding cancer cell ICAM-1 to monocyte β₂ integrins and binding endothelial ICAM-1 and VCAM-1 to monocyte β₁ and β₂ integrins. The results of this study imply that LPS is an important risk factor for cancer metastasis and that the elevated serum level of histamine further increases the risk of LPS-induced cancer metastasis. Preventing bacterial infections is essential in cancer treatment, and it is particularly vital for cancer patients affected by allergy.     

Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).