Miki Yasuhiro, Suzuki Takashi, Sasano Hironobu
Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken 980-8575, Japan.
J Steroid Biochem Mol Biol. 2007 Aug-Sep;106(1-5):97-101. doi: 10.1016/j.jsbmb.2007.05.007. Epub 2007 May 24.
Aromatase is a key enzyme of estrogen production through conversion from serum androgens in estrogen-dependent postmenopausal breast cancer. Aromatase has been reported to be predominantly located in intratumoral stromal cells and adipocytes but not in parenchymal or carcinoma cells in breast cancer tissue. It is, however, true that there have been controversies regarding intratumoral localization of aromatase in human breast carcinoma, especially whether intratumoral production of estrogens through aromatase occurs in parenchymal or stromal cells. Results of several studies suggested that aromatase present in parenchymal carcinoma cells plays more important roles in the growth and invasion of breast carcinomas than that in stromal cells through providing higher levels of estrogens to carcinoma cells. Aromatase inhibitors are increasingly being used in place of tamoxifen after results of various clinical trials demonstrated that aromatase inhibitors are more effective in increasing survival and recurrence of estrogen-dependent breast cancer patients. Therefore, it is important to clarify the estrogen supplying pathway by aromatase inside of breast carcinoma tissues in order to evaluate the possible efficacy of aromatase inhibitor treatment. In this review, the controversies regarding these intratumoral localization patterns in human breast carcinoma will be briefly summarized.
芳香化酶是雌激素依赖性绝经后乳腺癌中通过血清雄激素转化产生雌激素的关键酶。据报道,芳香化酶主要位于肿瘤内基质细胞和脂肪细胞中,而不在乳腺癌组织的实质细胞或癌细胞中。然而,关于人类乳腺癌中芳香化酶的肿瘤内定位确实存在争议,特别是通过芳香化酶在肿瘤内产生雌激素是发生在实质细胞还是基质细胞中。几项研究结果表明,与基质细胞中的芳香化酶相比,实质癌细胞中存在的芳香化酶通过为癌细胞提供更高水平的雌激素,在乳腺癌的生长和侵袭中发挥更重要的作用。各种临床试验结果表明,芳香化酶抑制剂在提高雌激素依赖性乳腺癌患者的生存率和降低复发率方面更有效,因此越来越多地被用于替代他莫昔芬。因此,明确乳腺癌组织内芳香化酶的雌激素供应途径对于评估芳香化酶抑制剂治疗的可能疗效很重要。在这篇综述中,将简要总结关于人类乳腺癌中这些肿瘤内定位模式的争议。