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.
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.
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.
Together, these results suggest that targeting mutant (V600E)B-Raf reduces melanoma cell extravasation by decreasing IL-8 production and interrupting ICAM-1-beta2 integrin binding of melanoma cells to the endothelium mediated by PMNs in the microcirculation, which provides a rationale and mechanistic basis for targeting mutant (V600E)B-Raf to inhibit melanoma extravasation and subsequent metastasis development.
To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue.
Thus, some host cytokines may preferentially induce melanoma cells to express ICAM-1 (which can increase host cytotoxic response against melanoma), other than the VnR (which instead might contribute to melanoma metastasis).
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.
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.
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.
These findings revealed that ICAM-1 gene transfection to cancer cells could be a useful immuno-gene therapy for the peritoneal metastasis of gastric carcinoma.
The purpose of this study was: (1) to test whether TNF-alpha-treated human melanoma cells are indeed more metastatic than untreated C8161 and (2) to determine whether ICAM-1 plays a role in metastasis of C8161.
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.
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.
Such TNF-induced NF-kappaB-regulated gene products involved in cellular proliferation [cyclooxygenase-2 (COX-2), cyclin D1, and c-myc], antiapoptosis [inhibitor of apoptosis protein (IAP)1, IAP2, X-chromosome-linked IAP, Bcl-2, Bcl-x(L), Bfl-1/A1, TNF receptor-associated factor 1, and cellular Fas-associated death domain protein-like interleukin-1beta-converting enzyme inhibitory protein-like inhibitory protein], and metastasis (vascular endothelial growth factor, matrix metalloproteinase-9, and intercellular adhesion molecule-1) were also down-regulated by curcumin.
Since decreased expression of ICAM-1 has been known to contribute to cancer cell escape from immunologic recognition and cytotoxicity by effector cells, the present results indicate that unknown function of TGF-beta1 in the tumor progression and metastasis of pancreatic cancer.
Serum soluble intercellular adhesion molecule 1 (sICAM-1) from patients with a benign HCC tumor, and the expression of ICAM-1 in the orthotopically transplanted LCI-D20 tumor of a nude mouse liver cancer metastasis model, and in human hepatoma, the tumor surrounding tissue and normal liver, was analyzed semiquantitatively by the immuno-dot blot method.
Secretory phospholipase A(2) (sPLA(2)) enzymes produce inflammatory mediators that stimulate ICAM-1 expression, and upregulation of PLA(2) activity can enhance metastasis.
Recently, a correlation between surface expression of ICAM-1 and secondary tumor formation by human melanomas has been described in several laboratories.
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.
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.