Ribeiro R, Lopes C, Medeiros R
Molecular Oncology Unit, Instituto Português de Oncologia, Edifício Laboratórios--PISO 4, R. Dr. Ant. Bernardino Almeida, 4200-072 Porto, Portugal.
Eur J Cancer Prev. 2004 Oct;13(5):359-68. doi: 10.1097/00008469-200410000-00002.
Leptin's relation with obesity has been clearly demonstrated while its role in oncobiology is still largely unknown. Epidemiological studies on serum leptin provide valuable though controversial data, while in vitro studies consistently show leptin's angiogenic and proliferative potential in cancer. Leptin's activity is mediated by tissue-specific receptors, differentially expressed in organs such as the prostate. The molecular cascades triggered by leptin result in prostatic cell proliferation and angiogenic activity, thus linking the hormone mainly to prostate cancer prognosis. This review also addresses leptin's metabolic interactions with cytokines, growth factors or hormones, establishing perceptive pathways leading to carcinogenesis or prostate cancer progression and metastasis. Better understanding of these mechanisms may help in the development of new and more effective treatments for prostate cancer. The consolidation of leptin molecular genetics profile in prostate cancer patients may help to create susceptibility groups in normal individuals, facilitating a preventive dietary intervention or strategies for chemoprevention. We hypothesize that the balance between androgen and leptin levels may facilitate the increase in the ratio of androgen-independent prostate cancer cells to androgen-dependent cells in the tumour.
瘦素与肥胖的关系已得到明确证实,但其在肿瘤生物学中的作用仍大多未知。关于血清瘦素的流行病学研究提供了有价值但存在争议的数据,而体外研究一致显示瘦素在癌症中具有血管生成和增殖潜力。瘦素的活性由组织特异性受体介导,这些受体在前列腺等器官中差异表达。瘦素触发的分子级联反应导致前列腺细胞增殖和血管生成活性,从而将该激素主要与前列腺癌预后联系起来。本综述还探讨了瘦素与细胞因子、生长因子或激素的代谢相互作用,建立了导致致癌作用或前列腺癌进展及转移的感知途径。更好地理解这些机制可能有助于开发新的、更有效的前列腺癌治疗方法。巩固前列腺癌患者的瘦素分子遗传学特征可能有助于在正常个体中创建易感群体,促进预防性饮食干预或化学预防策略。我们假设雄激素和瘦素水平之间的平衡可能有助于肿瘤中雄激素非依赖性前列腺癌细胞与雄激素依赖性细胞比例的增加。