Targeting secreted factors in endocrine resistant breast cancer therapy

摘要/总结： 各种类型的内分泌治疗已用于绝经后妇女的早期乳腺癌 癌这些疗法是安全有效的，但最初有反应的乳腺肿瘤通常会产生耐药性 并最终复发。由于肿瘤与肿瘤周围环境之间的交流在肿瘤发生发展中起着重要作用， 生长肿瘤并将肿瘤扩散到次级器官，我们检查了内分泌抵抗的传播， 具有基质的乳腺癌，基质是组织或器官的一部分，在乳腺癌中具有连接和结构作用。 癌我们建立了四种不同的内分泌抵抗乳腺癌细胞系，并检测了它们的表达。 这些细胞与四个基质细胞的通信。我们发现CCL 5和endoglin可能在 内分泌抵抗性乳腺癌中的作用。因此，我们将1）研究CCL 5和内皮糖蛋白在细胞凋亡中的作用。 ERBC细胞与基质细胞之间的相互作用; 2）揭示CCL 5和endoglin上调的机制 ERBC和基质之间的串扰，以及3）开发治疗策略以阻断旁分泌相互作用 间质细胞和ERBC细胞之间的关系。 我们将研究哪些分泌因子可以作为乳腺癌转变的关键调节因子 细胞内分泌抵抗和获得侵略性表型。此外，从细胞中分泌的因子 内分泌抵抗性乳腺癌和间质之间的沟通可能被证明是一个有吸引力的目标， 乳腺癌药物目前使用的大多数抗癌药物都是为了直接影响肿瘤而开发的 细胞这些药物对阻断来自肿瘤环境的信号作用不大。我们提议的调查 将给我们一个最强有力的信号的小列表。毒品，其中一些我们将在这里确认， 阻断这些信号可能会限制肿瘤扩散到继发性肿瘤的能力， 器官，这将导致患者的总体生存率提高。

Abstract/Summary: Various types of endocrine therapy have been used for postmenopausal women with early stage breast cancer. These therapies are safe and effective, but initially responsive breast tumors often develop resistance and eventually recur. Since a communication between tumor and tumor circumstance plays an important role to grow tumor and spread tumor to secondary organs, we examined the communication of endocrine resistant breast cancer with stroma which is the part of a tissue or organ that has a connective and structural role in cancer. We established four different endocrine resistant breast cancer cell lines and examined the communication of these cells with four stromal cells. We found that CCL5 and endoglin might play an important role in endocrine resistant breast cancer. Thus, we will 1) Investigate the role of CCL5 and endoglin in the crosstalk between ERBC cells and stromal cells, 2) Unveil the mechanism of the upregulated CCL5 and endoglin in crosstalk between ERBC and stroma, and 3) Develop therapeutic strategies to block the paracrine interaction between the stromal cell and ERBC cell. We will investigate which secreted factors could serve as a key regulator in the transition of breast cancer cells to endocrine resistance and gaining of an aggressive phenotype. Further, secreted factors from the communication between endocrine resistant breast cancer and stroma might prove to be an attractive target for breast cancer drugs. Most of the cancer drugs in use currently have been developed to directly impact tumor cells. These drugs do not do much to block signals coming from tumor circumstance. Our proposed investigation will give us a small list of the most potent of these signals. Drugs, some of which we will identify here, and others that will have to be developed, that block these signals could limit the ability of the tumors to spread to secondary organs, which should result in overall survival gains for patients.