Targeting secreted factors in endocrine resistant breast cancer therapy

摘要/摘要： 对早期乳房的绝经后妇女进行了各种类型的内分泌治疗 癌症。这些疗法是安全有效的，但最初有反应的乳腺肿瘤往往会产生耐药性。 并最终复发。由于肿瘤和肿瘤环境之间的沟通对 肿瘤生长和向次级器官扩散，我们检测了内分泌抵抗的沟通 有间质的乳腺癌，间质是具有连接和结构作用的组织或器官的一部分 癌症。我们建立了四个不同的内分泌耐药乳腺癌细胞系，并检测了 这些细胞与四个基质细胞之间的联系。我们发现CCL5和endoglin可能在 在内分泌抵抗乳腺癌中的作用。因此，我们将1)研究CCL5和endoglin在 ERBC细胞和基质细胞之间的串扰，2)揭示CCL5和endogline上调的机制 在ERBC和基质之间的串扰中，以及3)开发治疗策略来阻断旁分泌相互作用 在基质细胞和ERBC细胞之间。 我们将研究哪些分泌因子可能在乳腺癌的转移中起到关键的调节作用。 细胞对内分泌产生抵抗，并获得侵袭性表型。此外，来自于 内分泌耐药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开发出来直接影响肿瘤的 细胞。这些药物在阻断来自肿瘤环境的信号方面作用不大。我们建议进行的调查 会给我们一个最强信号的小名单。毒品，其中一些我们将在这里确定，以及其他 这将是必须开发的，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，这应该会导致患者的总体生存增加。

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.