Fatty Acid Modulation of Cancer Cell Spreading and Cytoskeleton Rearrangement
Tumor cell — extracellular matrix interactions consist of attachment, spreading, migration and digestion of matrix ligands. These interactions are critical determinants during metastasis (1,2) and are mediated by receptors consisting of integrins, cell adhesion molecules (CAM) and proteoglycans (3,4). The first step in matrix interaction is a passive phase characterized by initial ligand/receptor interactions, while the second step, the spreading process, is more complex and includes redistribution of matrix receptors, activation of the signal transduction pathways and rearrangement of the cytoskeleton (5). These events are prerequisites for subsequent tumor cell migration and matrix lysis. The regulatory mechanism(s) of cell spreading is not known. However, those mechanisms which control matrix receptor expression, e.g., TGFβ and other cytokines (i.g., IL-I, TNF) may be involved (6). Previous studies indicated that a 12-LOX metabolite of arachidonic acid (AA), 12-(S)-HETE, serves as a positive regulator of integrin αllbβ3 expression and function in murine tumor cells (7,8). However, it was not clear in these studies which phase (i.e., attachment or spreading) of tumor cell matrix interaction was affected by 12-(S)- HETE. Therefore we have analyzed the effects of 12-(S)-HETE on the spreading of tumor cells on a defined matrix protein, fibronectin (FN).
KeywordsCell Spreading B16a Cell Murine Tumor Cell Tumor Cell Spreading Extracellular Matrix Interaction
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