Breast Cancer Cell Motility Molecular Targets For Possible Antimetastatic Agents

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Insight into the molecular mechanisms of breast cancer cell motility has revealed a number of possible targets for the development of anti-metastatic drugs. Some of these targets were already indicated earlier in the text. In animal models for breast cancer metastasis, neutralizing antibodies against CXCR4 reduce the number of metastases (146). Furthermore, CXCR4 has been studied intensively in AIDS research, and CXCR4 antagonists from this research area such as T140, have shown to be capable of inhibiting cancer cell motility and pulmonary metastasis formation (147). In another study the synthetic inhibitor TN1 4003 was shown to reduce the number of metastasis in laboratory animals (148). Together with the RGD peptidomimetics already mentioned before, the CXCR4 antagonists are candidate molecules for anti-metastatic treatment. Cyclooxygenase-2 (COX-2) inhibitors have regained interest in oncology as well, since it was shown convincingly that they can inhibit cancer cell motility and invasion, and presumably metastasis formation by a mechanism that encompasses integrin adhesion and MMP production (29,149,150).

Other agents are currently being used in treatment and prevention of cancer, and, through a better knowledge of their action mechanisms, appear to reduce breast cancer motility and metastasis. Examples of such molecules are: the bisphosphonate zoledronic acid (151-153), the soy phytoestrogens genistein and daidzein (via NFkB) (154), green tea polyphenols (via uPA secretion) (155), modified citrus pectin (via galectin-3) (156) and the phytosterol P-sitosterol (via cell-matrix adhesion) (157). Still other molecules, like y-linoleic acid, are promising, because they inhibit cancer cell motility and angiogenesis (158).

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