Prostaglandin E2/EP1 Signaling Pathway Enhances Intercellular Adhesion Molecule 1 (ICAM-1) Expression and Cell Motility in Oral Cancer Cells

Abstract

Oral squamous cell carcinoma has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. However, the effects of COX-2 on human oral cancer cells are largely unknown. We found that overexpression of COX-2 or exogenous PGE 2 increased migration and intercellular adhesion molecule 1 (ICAM)-1 expression in human oral cancer cells. Using pharmacological inhibitors, activators, and genetic inhibition of EP receptors, we discovered that the EP1 receptor, but not other PGE receptors, is involved in PGE 2 -mediated cell migration and ICAM-1 expression. PGE 2 -mediated migration and ICAM-1 up-regulation were attenuated by inhibitors of protein kinase C (PKC)␦, and c-Src. Activation of the PKC␦, c-Src, and AP-1 signaling pathway occurred after PGE 2 treatment. PGE 2 -induced expression of ICAM-1 and migration activity were inhibited by a specific inhibitor, siRNA, and mutants of PKC␦, c-Src, and AP-1. In addition, migration-prone sublines demonstrated that cells with increased migration ability had higher expression of COX-2 and ICAM-1. Taken together, these results indicate that the PGE 2 and EP1 interaction enhanced migration of oral cancer cells through an increase in ICAM-1 production.

Prognostic value of intercellular adhesion molecule (ICAM)-1 expression in breast cancer

“…ICAM-1 expression is stimulated in tumour cells by various oncogenic stimuli via NFjB and AP-1 transcription factors, leading to an enhanced cell motility (Ahmed and Kundu 2010;Yang et al 2010) and invasive potential (Rosette et al 2005). In addition, ICAM-1 is expressed in endothelial cells which is corroborated by our immunohistochemical results (Fox et al 1995;Ksiazek et al 2010).…”

JNK/ERK/FAK Mediate Promigratory Actions of Basic Fibroblast Growth Factor in Astrocytes via CCL2 and COX2

“…Our study implicates CCL2 and COX2 in the autocrine regulation of astrocyte migration. While CCL2 is a paradigmatic chemotactic agent acting via its receptor CCR2, the mechanisms underlying the promigratory actions of COX2 remain undetermined, although they may involve the interaction of the prostaglandin E 2 with receptor EP1 [67] .…”

MIEN1 promotes oral cancer progression and implicates poor overall survival

“…3 Extensive research demonstrates the importance of various oncogenes and tumor suppressors along with associated signal transduction pathways in oral cancer progression. [5][6][7][8][9] It is evident that many of these pathways converge to facilitate invasion and migration of cells to the lymph nodes, characteristic of OSCC. Migration and invasion of cancer cells are hallmarks of cancer metastasis, 10,11 facilitated by processes including loss of cell adhesion and epithelial properties, cytoskeletal rearrangement, gain of mesenchymal form and ability to cleave the extracellular matrix by secreting proteases, and formation of new blood vessels by secreting angiogenic factors.…”