雌激素直接促进表达雌激素受体α（ERα）乳腺癌的生长。然而，在肿瘤微环境中基质表达ERα对雌激素的促肿瘤作用具有什么样的贡献从未被探索。
近来，发表在Cancer Research杂志上一则新项研究中，研究人员探讨了了17β-雌二醇（E2）影响肿瘤微环境和调节ERα阴性肿瘤发展的细胞和分子机制。科学家选用不同的ER阴性肿瘤细胞移植到同系免疫去势小鼠皮下，结果发现素E2促进肿瘤的生长，增加肿瘤内血管密度，并促使肿瘤血管趋向更健全的组织结构状态，从而改善血管的稳定，最终防止肿瘤缺氧和坏死。
E2的这些效果能被ERα缺陷小鼠完全抑制，表明宿主的ERα起到关键作用。值得注意的是，当Tie2表达阳性细胞缺失ERα后，E2并没有加速肿瘤的生长，即使在小鼠给予野生型骨髓移植后，E2也不能加速肿瘤细胞生长。总之，研究结果表明E2通过激活基质环境中的ERα，促进ERα的阴性肿瘤细胞的生长。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-3768
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Stromal Estrogen Receptor-α Promotes Tumor Growth by Normalizing an Increased Angiogenesis
Christel Péqueux, Isabelle Raymond-Letron, Silvia Blacher, Frédéric Boudou, Marine Adlanmerini, et al.
Estrogens directly promote the growth of breast cancers that express the estrogen receptor α (ERα). However, the contribution of stromal expression of ERα in the tumor microenvironment to the protumoral effects of estrogen has never been explored. In this study, we evaluated the molecular and cellular mechanisms by which 17β-estradiol (E2) impacts the microenvironment and modulates tumor development of ERα-negative tumors. Using different mouse models of ER-negative cancer cells grafted subcutaneously into syngeneic ovariectomized immunocompetent mice, we found that E2 potentiates tumor growth, increases intratumoral vessel density, and modifies tumor vasculature into a more regularly organized structure, thereby improving vessel stabilization to prevent tumor hypoxia and necrosis. These E2-induced effects were completely abrogated in ERα-deficient mice, showing a critical role of host ERα. Notably, E2 did not accelerate tumor growth when ERα was deficient in Tie2-positive cells, even in mice grafted with wild-type bone marrow. These results were extended by clinical evidence of ERα-positive stromal cell labeling in the microenvironment of human breast cancers. Together, our findings therefore show that E2 promotes the growth of ERα-negative cancer cells through the activation of stromal ERα (extra-hematopoietic Tie-2 positive cells), which normalizes tumor angiogenesis and allows an adaptation of blood supply to tumors, thereby preventing hypoxia and necrosis. These findings significantly deepen mechanistic insights into the impact of E2 on tumor development with potential consequences for cancer treatment.
