2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38836Breast cancer stem cells (BCSCs) have been identified as a subpopulation of breast cancer cells with markers of CD24-CD44+ or aldehyde dehydrogenase activity high (ALDH+) and have been proved to be associated with radiation resistance and metastasis. We have established several xenograft human breast cancer cells from patients in immunocompromised NOD/SCID mice and the BCSC population within these cells has been identified by surface markers CD24 and CD44 and intracellular ALDH activity. The established xenograft human breast cancer cells will be very useful in the investigation of biological properties of BCSCs. Heat shock proteins (Hsps) are a group of proteins which are induced expression after stress to serve as a chaperone for maintenance of corrected protein folding. Hsps have been reported to be overexpressed in many cancers and function as apoptosis inhibitor to maintain survival of cancer cells. In breast cancer study, several Hsps have been reported to be associated some clinicopathological factors. For example, the expression of Hsp27 was a risk factor of malignant progression in benign proliferating breast lesions. Cytoplasmic Hsp70 expression was linked to lymph node metastasis and poor differentiation of breast cancer. High expression of Hsp90a was positively correlated with early recurrence and negatively correlated with overall survival of breast cancer patients. However, the link between BCSCs and these Hsps remains unknown. Specific Aim 1 of this project is to investigate the expression and activation status of Hsp27, Hsp70 and Hsp90a between BCSCs and non-BCSCs. The upstream signaling of these Hsps in BCSCs will be identified further. Specific Aim 2 is to explore the biological functions of Hsp27, Hsp70 and Hsp90a in BCSCs, especially in the maintenance, cell survival, migration and invasion properties of BCSCs. Specific Aim 3 is to investigate the effect of these Hsps in the tumorigenicity and metastatic property of BCSCs in vivo. Based on the knowledge obtained from this project, the molecular mechanisms of Hsp27 in biology of BCSCs can be clarified and the results will provide the basic information on breast cancer therapy which target BCSCs.乳癌幹細胞是存在於乳癌細胞中一群特殊的細胞，目前認為這群細胞是乳癌的源頭，並與乳癌產生抗藥性以及轉移有密切的關係。過去我們在實驗室中從乳癌病人檢體建立了能夠在免疫不全小鼠乳腺形成腫瘤的乳癌細胞株，並以細胞表面分子CD24、CD44的表現或細胞內乙醛去氫酶(aldehyde dehydrogenase)活性成功鑑定出這些乳癌細胞株中的乳癌幹細胞群。這些來自於臨床乳癌病人的乳癌細胞株將是研究乳癌幹細胞的利器。熱休克蛋白(heat shock protein, Hsp)為細胞遭受熱或化學刺激時會大量表現的蛋白，其功能原與維持細胞內蛋白正常結構有關，在腫瘤研究中發現某些Hsps常會過度表現在許多種的癌細胞中，通常能抑制腫瘤細胞的細胞凋亡，因此被認為與腫瘤的生成有關。在乳癌的研究中，Hsp27、Hsp70以及Hsp90a都已有報導證實與一些乳癌臨床病理因子有相關性，例如Hsp27的表現與良性增生乳房組織的癌化進程有正相關；細胞質內Hsp70的表現與乳癌淋巴轉移及分化不全有關；Hsp90a的高表現與乳癌病人總存活率成負相關。然而，這些Hsps與乳癌幹細胞的關係仍無文獻報告。本研究計畫的第一項特定目標是探討乳癌幹細胞內三種Hsps的表現以及活化程度，並釐清Hsps活化所參與的訊息傳遞分子。第二項特定目標為了解三種Hsps在乳癌幹細胞內所扮演的功能性角色，尤其是對細胞存活、細胞移動以及侵入性的影響。第三項特定目標則是藉由動物實驗研究三種Hsps對於乳癌幹細胞在活體內形成腫瘤能力的影響，以及活體內癌症轉移的角色。透過本研究計畫的結果，將可以了解此三種Hsps在乳癌幹細胞中的生物學角色，以及所參與的分子機制，提供針對乳癌幹細胞特異性療法的基礎知識。 表乳癌乳癌幹細胞熱休克蛋白breast cancerbreast cancer stem cellsheat shock proteinsProject