ASCs介导的CNGRC肽靶向杀伤乳腺癌干细胞微血管龛内皮细胞的分子机制研究

Recurrence and metastasis of breast cancer, which is due to the self-renewal and differentiation potential of breast cancer stem cells, is one of the main challenges of the current clinical treatment. Cancer stem cell niche, which is mainly formed by microvessels, plays a critical role in the regulation of the number and function of cancer stem cells, and thus is closely related to the occurrence, development and metastasis of cancer. Destruction of cancer stem cell niche can lead to the eradication of cancer stem cells. Based on the above theory, our group have designed a kind of peptide (CisoDGRC peptide and CNGRC peptide) contained NGR and isoDGR sequence, which can specifically target and destroy the vascular endothelial cells and specifically penetrate the membrane of breast cancer cells. Adipose-derived stem cells (ASCs) are used as the carrier acording to their homing property. The polypeptide is delivered to the vascular endothelial cells of cancer stem cell niche and destroies it, subsequently eradicates the cancer stem cells and finally inhibit the growth of cancer cells.

乳腺癌的复发转移是目前临床治疗的主要难题之一。目前研究认为与乳腺癌干细胞的自我更新及分化功能有关。肿瘤微血管所形成的肿瘤干细胞龛对于肿瘤干细胞的数量及功能的调节发挥着重要的作用，从而与肿瘤的发生、发展及转移密切相关，破坏肿瘤干细胞龛中的微血管可能可以达到消灭肿瘤干细胞的目的。基于以上理论，本课题组根据以往筛选出的穿膜肽的结构规律，自行设计了一种具有NGR和isoDGR序列、可特异性定向杀伤血管内皮细胞、并针对乳腺癌细胞具有特异性穿膜能力的多肽：CisoDGRC肽及CNGRC肽，并以脂肪源性干细胞（ASCs）为载体，利用其归巢性，使这种多肽定位于肿瘤干细胞龛的血管内皮细胞，通过破坏肿瘤干细胞赖以生存的微血管龛，最终达到清除肿瘤干细胞的自我更新和分化特性，抑制肿瘤细胞生长的目的。

乳腺癌的复发转移是目前临床治疗的主要难题之一。目前研究认为与乳腺癌干细胞的自我更新及分化功能有关。肿瘤微血管所形成的肿瘤干细胞龛对于肿瘤干细胞的数量及功能的调节发挥着重要的作用，从而与肿瘤的发生、发展及转移密切相关，破坏肿瘤干细胞龛中的微血管可能可以达到消灭肿瘤干细胞的目的。基于以上理论，本课题组根据以往筛选出的穿膜肽的结构规律，自行设计了一种具有NGR和isoDGR序列、可特异性定向杀伤血管内皮细胞、并针对乳腺癌细胞具有特异性穿膜能力的多肽：CisoDGRC肽及CNGRC肽，并以脂肪源性干细胞（ASCs）为载体，利用其归巢性，使这种多肽定位于肿瘤干细胞龛的血管内皮细胞，通过破坏肿瘤干细胞赖以生存的微血管龛，最终达到清除肿瘤干细胞的自我更新和分化特性，抑制肿瘤细胞生长的目的。