乳腺癌是女性最常见的恶性肿瘤之一，且复发率高。现普遍认为乳腺癌干细胞是逃逸常规治疗并导致复发的主要原因。因此，以乳腺癌干细胞为靶点的治疗已成为研究热点。本项目前期研究结果提示肿瘤微环境中的透明质酸可在多方面影响乳腺癌的发生、发展和转移。透明质酸的减少，可降低乳腺癌细胞的迁移、黏附、和增殖能力，以及降低乳腺癌干细胞的比例和干细胞分子标志物的表达。据此我们提出一种新的假设，即乳腺癌肿瘤微环境中透明质酸的减少会破坏乳腺癌干细胞的干性，以减缓乳腺癌的发生、发展和转移。本项目中我们将采用海藻酸钙凝胶球3D培养体系，模拟乳腺癌细胞在体内的生长环境，应用细胞培养和动物模型，研究乳腺癌肿瘤微环境中的透明质酸对乳腺癌干细胞干性的影响及调控机制。本项目将更好地了解肿瘤微环境对肿瘤干细胞的影响机制，为以肿瘤干细胞为靶点的治疗方法提供前沿性理论基础，进一步促进以肿瘤干细胞进行靶向治疗领域的发展。

Breast cancer is a common malignant tumor in females with a significantly high recurrence rate. Breast cancer stem cells (SCs) play a major role in the high recurrence rate because SCs escape routine radiation treatment and chemotherapy. Therefore, development of new cancer therapies directed specifically at SCs become increasingly important. Our preliminary results indicate that a low level of hyaluronan (HA) within the tumor microenvironment inhibits breast cancer migration, adhesion properties, and proliferation. Furthermore, a low level of HA reduces the SC population and the expression of SC markers. Based on the above findings, we propose a new theory that low levels of HA within the tumor microenvironment affects the SC stemness such that the occurrence, progression, and metastasis of breast cancer are reduced. In this project, we will study the effect of HA on the properties of SCs and relevant regulatory signal pathways by culturing breast cancer cells in alginate beads in order to mimic the in vivo tumor microenvironment. Our research elucidates the role of the tumor microenvironment on SCs and thereby provides a basis for new cancer therapies that target specific components of the tumor microenvironment.