利用具有特定奈米片段及彈性的生醫材料去除癌症幹細胞

Depletion of Colon Cancer-Initiating Cells on Biomaterials Having Specific Nanosegments and Elasticity

周育瑄(Yu-Hsuan Chou)

指導教授 ： 樋口亞紺

國立中央大學/工學院/化學工程與材料工程學系/碩士(2014年)

摘要

癌症起始細胞或癌症幹細胞 （癌幹細胞）表現自我更新的能力，並負責腫瘤生成。癌幹細胞是一種幹細胞會生成腫瘤，並表現出幹細胞特性，例如自我更新和分化為多種細胞類型的能力的幹細胞。癌幹細胞在腫瘤中作為一個獨特的群體，並導致腫瘤生成從而形成復發和轉移。針對癌幹細胞的特殊療法的發展可能提高生存率和癌症患者的生活品質，特別是那些深受腫瘤轉移疾病之苦的患者。研究者提出了許多標記抗體來辨識癌幹細胞，例如：CD29，CD133，Lgr5，Msi-1，ALDH-1等。然而，專一且可信任的標記抗體來辨識大腸癌細胞尚未確定。唯一可靠的方法來識別和量化癌幹細胞是透過觀察動物體內實驗腫瘤的產生。本研究將大腸癌細胞培養在具有不同軟硬度的細胞外間質衍生之寡肽的水凝膠上，評估癌幹細胞是否增加（純化）或減少（耗竭）。癌幹細胞能透過培養在Pluronic接枝的基底上被耗盡，且於動物體內實驗沒有腫瘤生成，相反地，癌幹細胞會存活在具有不同軟硬度的細胞外間質衍生之寡肽的水凝膠上，且於動物體內實驗生成腫瘤。此外，本研究亦利用服樂癌注射劑來辨識癌幹細胞，從研究成果發現體外培養與動物體內實驗呈現相同的趨勢。本研究提出一種特殊的生醫材料Pluronic，當大腸癌細胞培養在Pluronic接枝的盤子上可以耗盡癌幹細胞，而癌幹細胞卻可以在具有不同軟硬度的細胞外間質衍生之寡肽的水凝膠上存活或增加。

關鍵字

癌症幹細胞

並列摘要

Cancer-initiating cells or cancer stem cells (CSCs) exhibit a self-renewing capacity and are responsible for tumor generation. CSCs are stem cells that form tumors and exhibit stem cell properties, such as self-renewal and the ability to differentiate into multiple cell types. It was suggested that CSCs persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. The development of specific therapies targeted at CSCs may improve the survival rates and the quality of life of cancer patients, particularly those suffering from metastatic disease. Several markers for colon CSCs have been proposed: CD24, CD29, CD44, CD133, CD166, Lgr5, Muc2, ESA, Msi-1, and ALDH-1. However, specific and reliable surface markers of colon CSCs have not been identified. The only reliable method to identify and quantify CSCs is the observation of tumor generation in the serial xenotransplantation model. In this study, the Colo205 and LoVo colon cancer cell lines and colon cancer cells established from the cells of colon cancer patients (Primary-colon cancer cells 0317) were cultured on ECM (nanosegment)-grafted, oligopeptide (nanosegment)-grafted, and Pluronic (nanosegment)-grafted dishes having different elasticity (100 kPa to 16 MPa elasticity) as well as tissue culture dishes (TCPS, 10GPa elasticity). The oligopeptide-grafted dishes were prepared from polyvinylalcohol-co-itaconic acid (PVA-IA) coating dishes grafted with several nanosegments (KGGPQVTRGDVFTMP [cell-binding domain derived from vitronectin, oligoVN], GGNGEPRGDTYRAY [cell-binding domain from bone sialoprotein, oligoBSP], and GKKQRFRHRNRKG [heparin-binding domain, oligoHBD]). We evaluated whether the CSCs were enhanced (purified) or decreased (depleted) among the colon cancer cells after the colon cancer cells were cultured on ECM-grafted, oligopeptide-grafted, TCPS, or Pluronic-grafted dishes. The ratio of the CSCs was evaluated from the tumor generation of cancer cells in mice that were subcutaneously xenotransplanted into mice. CSCs in colon cancer cells could be selectively depleted from colon cancer cells (Colo205, LoVo, and Primary-colon cancer cells) when they were cultured on Pluronic-grafted dishes having optimal elasticity, whereas CSCs were maintained on TCPS and extracellular matrix (ECM)-immobilized dishes as well as oligopeptide-immobilized dishes. Furthermore, there is no tumor generation of colon cancer cells cultured on pluronic-grafted dishes while there is tumor generation of colon cancer cells cultured on oligopeptide-immobilized dishes. On the other hand, anticancer drug (5-Fluorouracil) was used as well to identify CSCs in colon cancer cells. The results show the same tendency in in vitro cultivation and in vivo experiment. It was concluded that the pluronic-grafted dishes deplete cancer-initiating cells (CSCs) from colon cancer cells while CSCs in colon cancer cells remain or enhance on TCPS and oligopeptide-immobilized dishes, which was explained by specific biomedical characteristics of Pluronic.

並列關鍵字

Colon Cancer-Initiating Cells

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