Cos Samuel, Alvarez-García Virginia, González Alicia, Alonso-González Carolina, Martínez-Campa Carlos
Department of Physiology and Pharmacology, School of Medicine, University of Cantabria and Valdecilla Research Institute, Santander 39011, Spain.
Oncol Lett. 2014 Aug;8(2):487-492. doi: 10.3892/ol.2014.2203. Epub 2014 May 30.
Melatonin, the main secretory product of the pineal gland, is an oncostatic agent that reduces the growth and development of various types of tumors, particularly mammary tumors whose growth is dependent on estrogens. Previous and studies point to the hypothesis that melatonin interplays with estrogen signaling pathways at three different levels: i) an indirect mechanism, by interfering with the hypothalamic-pituitary-reproductive axis in such way that the level of plasma estrogens synthesized by the gonadal glands are downregulated; ii) a direct mechanism of the pineal gland at the cell cancer level, disrupting the activation of estradiol receptors, therefore behaving as a selective estrogen receptor modulator; and iii) by regulating the enzymes involved in the biosynthesis of estrogens in other tissues, thus behaving as a selective estrogen enzyme modulator. The intratumoral metabolism and synthesis of estrogens, as a result of the interactions of various enzymes, is more important than blood uptake to maintain mammary gland estrogen levels in menopausal females. Additionally, estrogens are considered to play an important role in the pathogenesis and development of hormone-dependent breast carcinoma. Paracrine interactions among malignant epithelial cells and proximal adipose and endothelial cells, through cytokines and growth factors produced by breast tumor cells, modulate estrogen production at the mammary tumor level and, as a consequence, the genesis and development of mammary tumors. The aim of the present review is to summarize the recent findings describing the mechanisms by which melatonin is able to modulate the crosstalk among malignant epithelial, endothelial and adipose cells in breast cancer.
褪黑素是松果体的主要分泌产物，是一种肿瘤抑制因子，可抑制各类肿瘤的生长和发展，尤其是生长依赖雌激素的乳腺肿瘤。以往的研究提出了这样一种假说，即褪黑素在三个不同水平上与雌激素信号通路相互作用：i）一种间接机制，通过干扰下丘脑 - 垂体 - 生殖轴，下调性腺合成的血浆雌激素水平；ii）松果体在细胞癌水平的直接作用机制，破坏雌二醇受体的激活，因此表现为一种选择性雌激素受体调节剂；iii）通过调节其他组织中参与雌激素生物合成的酶，从而表现为一种选择性雌激素酶调节剂。在绝经后女性中，由于各种酶的相互作用，雌激素在肿瘤内的代谢和合成对于维持乳腺雌激素水平比血液摄取更为重要。此外，雌激素被认为在激素依赖性乳腺癌的发病机制和发展中起重要作用。恶性上皮细胞与近端脂肪和内皮细胞之间通过乳腺肿瘤细胞产生的细胞因子和生长因子进行旁分泌相互作用，调节乳腺肿瘤水平的雌激素产生，进而影响乳腺肿瘤的发生和发展。本综述的目的是总结近期关于褪黑素调节乳腺癌中恶性上皮、内皮和脂肪细胞之间相互作用机制的研究发现。
