Cell migration is controlled by several mechanisms, including complex interactions between the tumour and its stroma. Therefore, much effort is currently directed at understanding the biological mechanisms of the invasive behaviour of oral cancers. A typical feature of these tumours is that they spread largely through progressive local invasive growth. Oral cancers, the majority of which are squamous cell carcinomas, are aggressive neoplasms associated with serious morbidity and considerable mortality. The results demonstrate LPA-stimulated migration in oral carcinoma cells through LPAR3, mediated further by PKC, which acts either in concert with or independently of EGFR transactivation. In D2 cells, LPA induced EGFR transactivation, but this was associated with slowing of a very high inherent migration rate in these cells. However, while LPA induced transactivation of EGFR and the stimulated migration was blocked by EGFR inhibitors in E10 cells, LPA did not induce EGFR transactivation in SCC-9 cells. Furthermore, in both these cell lines, the stimulation by LPA was dependent on PKC activity. The receptor expression profile and the effects of specific pharmacological antagonist and agonists indicated that LPA-stimulated cell migration was mediated through LPAR3 in E10 and SCC-9. LPA stimulated cell migration in the two oral carcinoma cell lines E10 and SCC-9, but was slightly inhibitory in D2. Activation of signalling proteins was examined with Western blotting and isoelectric focusing, and signalling mechanisms were further explored using pharmacological agents and siRNA directed at specific receptors and pathways. Protein and mRNA expression of LPA receptors was studied with Western blotting and qRT-PCR. Cell migration was studied in a scratch wound assay, and invasion was demonstrated in organotypic three dimensional co-cultures.
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The oral carcinoma cell lines E10, SCC-9, and D2 were investigated. The signalling mechanisms of LPA are not fully understood, and in oral carcinoma cells the specific receptors and pathways involved in LPA-stimulated migration are unknown. Although LPA is predominantly promigratory, some of the receptors may have antimigratory effects in certain cells. LPA is present in most tissues and can activate cells through six different LPA receptors (LPAR1-6).
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Lysophosphatidic acid (LPA) is involved in a number of biological processes, and may have a role in cancer cell migration and invasiveness. Oral squamous cell carcinoma is an aggressive neoplasm with serious morbidity and mortality, which typically spreads through local invasive growth.