Lipoxygenase metabolites and cancer metastasis.

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Cancer metastasis is a complicated process. For a transformed cell to form a successful metastatic colony, it must in general complete all or most of the well-defined steps that comprise the “metastatic cascade”.1–4 The first step is uncontrolled cell proliferation, characteristic of both benign and malignant tumor cells. Intrinsic or acquired genetic instability, together with various epigenetic factors, generate tumor cell variants that acquire unique phenotypic characteristics that dissociate them from the parent tumor population and thus allow these variants to escape from the “social” constraints imposed by the host. This step confers on these “mutated” tumor cells invasive or metastatic capabilities and is generally considered to be the first step leading to site-specific metastasis. In the next step, tumor cells, in response to various chemoattractants and cytokines derived from the host and/or tumor cells, migrate towards neighboring vasculature or intravasate into the vasculature of the tumor and thus enter the hematogenous or lymphatic circulation. Subsequently, tumor cells travel to and arrest in the microcirculation by specific adherence to the endothelial cells of the target organ. Thereafter, tumor cells induce endothelial cell retraction, exit from circulation (extravasation), interact with the organ-specific extracellular matrix (ECM), proliferate in response to local (“soil”) growth factors, and finally form a metastatic colony. Failure at any one of these steps generally will abort the metastatic process. Completion of every step of the metastatic cascade is subject to a multitude of variable influences, an apparent example being the requirement of angiogenesis for the growth of both primary and secondary tumors.5.6 KeywordsCancer MetastasisTumor Cell AdhesionBioactive LipidMurine Melanoma CellTumor Cell MotilityThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.