Role of ICAM1 in invasion of human breast cancer cells

Abstract

We identified previously a region on chromosome 19p13.2 spanning the genes encoding the intercellular adhesion molecules (ICAM), ICAM1, ICAM4 and ICAM5 as a breast cancer susceptibility locus. Genetic variants in this region were also associated with indicators of disease severity, including higher rates of metastases to other organs. Based on this association, we set out to explore the role of ICAM1 in proliferation and invasion of human breast cancer cells. We observed that ICAM1 downregulation at the mRNA and protein levels led to a strong suppression of human breast cell invasion through a matrigel matrix. Under the same conditions, no significant effect on cell proliferation in vitro was seen. Incubation of cells with an antibody against ICAM1 blocked invasion of the highly metastatic MDA-MB-435 cell line in a dose-dependent manner without affecting cell migration. We also demonstrated that the level of ICAM1 protein expression on the cell surface positively correlated with metastatic potential of five human breast cancer cell lines and that ICAM1 mRNA levels were elevated in breast tumor compared with adjacent normal tissue. These results corroborate our previous genetic finding that variations in the ICAM region are associated with the occurrence of metastases and establish a causal role of ICAM1 in invasion of metastatic human breast carcinoma cell lines.

Lactobacillus plantarum Lipoteichoic Acid Alleviates TNF-α-Induced Inflammation in the HT-29 Intestinal Epithelial Cell Line

“…LTA inhibited rhTNF-α-mediated THP-1 cell adhesion to HT-29 Adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are implicated in cancer progression (O'Hanlon et al, 2002;Rosette et al, 2005). In this study, the effect of pLTA on the TNF-α-induced expression of adhesion molecules was examined.…”

“…TNF-α and nitric oxide (NO) trigger colonic inflammation and carcinogenesis in a Helicobacter hepaticus-infected mouse model, indicating that inflammation mediated by elevated TNF-α and NO causes colon carcinogenesis (Erdman et al, 2009;Kolios et al, 1996). Adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), are also implicated in cancer progression (O'Hanlon et al, 2002;Rosette et al, 2005).…”

Effects of Raf Kinase Inhibitor Protein Expression on Metastasis and Progression of Human Breast Cancer

“…The transwell chambers were incubated at 37°C in 5% CO 2 humidified atmosphere for 48 h. The cells that had not invaded were removed from the upper face of the filters using cotton swabs. The cells that had invaded to the lower surface of the filters were fixed and stained in 0.1% crystal violet (23), and quantified by counting the numbers of cells that penetrated the membrane in five microscopic fields (at ×100 magnification) per filter. The experiment was repeated thrice.…”

ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB

“…ICAM molecules may target and block tumor progression by stimulation of an immune response such as leukocyte activation (15,16). Conversely, other investigations have shown that ICAM molecules are involved in cancer malignancy because their increased expressions are associated with a poor diagnosis, lower survival rates and metastasis in some cancers including melanoma, breast cancer and leukemia (17)(18)(19)(20)(21)(22)(23)(24). We have also reported that an increase of ICAM-3 expression in several cancer cells and specimens of cervical cancer patients induced enhanced radio-resistance by the activation of focal adhesion kinase (FAK) (25) and promoted cancer cell proliferation by the activation of Akt and p44/42 MAPK (26).…”