Quantitative real-time PCR and immunofluorescence staining indicated that the adhesion molecules ICAM-1 (CD54) and E-selectin (CD62E) can be significantly induced by intralesional application of TNF alpha in tissue from human melanoma metastases either in vitro or in vivo when grafted onto immunodeficient NSG (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ) mice that preserved human vessels.
The cytokine-mediated upregulation of metastasis- and inflammatory-associated genes, which are downstream genes of STAT3 including the intercellular adhesion molecule-1, matrix metalloproteinase-9, inducible nitric oxide synthase, and cyclo-oxygenase 2 (COX-2), were also significantly abolished by myricetin treatment.
Our study shows that the expression of the cell-cell and cell-matrix adhesion molecules ICAM-1, E-cadherin, periostin and MK was not significantly linked to metastatic disease in PDACs.
We also present evidence showing that tumor cell-derived IL-6 facilitates glycolytic metabolism in tumor cells by activating the MEK/ERK1/2/hypoxia-inducible transcription factor-1α (HIF-1α) pathway and increases lung colonization by OS cells by upregulating expression of intercellular adhesion molecule-1 (ICAM-1), enhancing tumor metastasis.
Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by ( a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), ( b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); ( c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), ( d) notable reduction in expression of inflammation-( IL1b, NFκB), angiogenesis-( VEGF) and metastasis-( MMP9, ICAM1) related genes; and ( e) higher immune response (high number of CD<sup>+</sup>4, CD<sup>+</sup>8, NK1.1 T cells in spleen).
The majority of studies to date have focused on the expression of the ICAM-1 on the surface of tumor cells, without research into ICAM-1 expression at sites of metastasis.
These results demonstrate that FBXO4 is a major regulator of ICAM-1 stability and that alterations in the stability of ICAM-1 can influence therapeutic outcome in metastatic cancer.
We developed a third-generation chimeric antigen receptor (CAR) targeting ICAM-1 to leverage adoptive T-cell therapy as a new treatment modality.<b>Experimental Design:</b> ICAM-1 CAR T cells were applied to multiple malignant and nonmalignant target cells to investigate specific target cell death and "off-tumor" toxicity <i>in vitro</i><i>In vivo</i> therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models established from a cell line and patient-derived tumors that rapidly develop systemic metastases.<b>Results:</b> ICAM-1 CAR T cells demonstrated robust and specific killing of PTC and ATC cell lines <i>in vitro</i> Interestingly, although certain ATC cell lines showed heterogeneous levels of ICAM-1 expression, addition of cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell lines became targetable.
When examined <i>in vivo</i> for the expression of biomarkers associated with cell survival (cIAP-1, Bcl-2, and survivin), proliferation (Ki-67 and cyclin D1) and metastasis (ICAM-1 and VEGF), all were down-modulated.
Fractalkine/CX3CL1 induced intercellular adhesion molecule-1-dependent tumor metastasis through the CX3CR1/PI3K/Akt/NF-κB pathway in human osteosarcoma.
Consistent with its regulatory role in NF-κB pathway, knockdown of DEPDC1 caused significant upregulation of A20 and downregulation of mutiple NF-κB downstream target genes implicated in proliferation and tumorigenesis (c-Myc, BCL2, CCND1, CCNB1 and CCNB2), and metastasis (MMP2, MMP9, ICAM1, vimentin, Twist1).
Intercellular adhesion molecule 1 (ICAM-1) protein is an important adhesion molecule that facilitates metastasis on one hand, and on the other hand supports the immunological synapse necessary for T-cell mediated elimination.
These results implying that ICAM-1 might be involved in the progression of breast cancer metastasis and lentivirus-mediated silencing of ICAM-1 might be a potential therapeutic approach for the treatment of breast cancer.
Intercellular adhesion molecule-1 (ICAM-1), a major molecule in stabilising cell-cell and cell-extracellular matrix interactions, is overexpressed and has crucial roles in tumour metastasis.
Secretory phospholipase A(2) (sPLA(2)) enzymes produce inflammatory mediators that stimulate ICAM-1 expression, and upregulation of PLA(2) activity can enhance metastasis.