2010-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658817摘要：骨調素(Osteopontin, OPN, spp1)是高度酸性磷酸化分泌性糖蛋白，最初由骨組織中分離所得，屬非膠原的骨基質蛋白。 OPN 不僅是細胞外基質，也是淋巴細胞和巨噬細胞的趨化和粘附分子，具有許多生理和病理上的功能：包括(1)促進B 淋巴細胞激活，(2)調節骨的形成，(3)促進巨噬細胞粘附和聚集，(4)促進平滑肌細胞遷移及抑制細胞凋亡，及(5)在發炎過程中維持組織通透性等多種功能。雖然學者們對OPN 已經有許多年研究的歷史，但是OPN 在細胞生長、血管新生、細胞黏附功能、腫瘤轉移的影響和其調節的機轉仍然不甚明白。因此本計畫的主要目的是：(1)利用細胞培養系統與不同細胞株 (3T3、EAhy926、RAW264.7、HUVEC、HEKn 等) 探討OPN 對細胞功能，如細胞增生、移行、細胞死亡、與血管新生、細胞黏附等，的in vitro 效應，並探究其機轉；細胞功能的改變並以細胞生物學及形態學的方法來檢驗 (2) 利用活體動物實驗探討Osteopontin 對傷口的癒合的效應，並以組織學、免疫染色技術、電子顯微鏡術等觀察其改變，及(3) 探討OPN對癌化細胞的生長、移行和轉移能力等in vitro 效應，並將腫癌細胞(癌化細胞株K7M2‐WT 及OPN‐down regulated K7M2‐shOPN)種入裸鼠體內以引發腫瘤之發生，觀察OPN 對癌化細胞的效應。吾人希望本計畫完成後可以增進吾人對OPN 在細胞或是動物生理反應中所扮演的角色更加了解，使OPN 對於傷口癒合或是癌症治療有些許貢獻。<br> Abstract: Osteopontin(OPN), also known as secreted phosphoprotein 1 (SPP1), is a highly acidicphosphorylated secretory glycoprotein and first identified in in osteoblasts. It is thenon-collagen bone matrix protein. OPN is not only the extracellular matrix, but also is thechemotactic and the adhesion molecule for lymphocytes , macrophages, and many other celltypes. OPN plays many physiological and the pathological functions, including: (1)promotes B lymphocyte activation, (2) regulates the bone formation, (3) promotes adhesionand accumulation of macrophages, (4) promotes migration and inhibits apoptosis in smoothmuscle cell, and (5) maintains the tissue permeability in the inflammatory process, etc.Although OPN has been studied for many years since 1986, howerer, the effect of OPN oncell growth, angiogenesis, cell adhesion, and tumor metastasis, as well as their underlyingmechanisms remain unclear.The purposes of this project are: (1) to investigate the in vitro effect of OPN on thecellular functions, such as proliferation, migration, cell death as well as angiogenesis andcell adhesion by using cell culture system and various cell lines (including 3T3, EAhy926,RAW264.7, HUVEC, HEKn etc.,); alteration of cellular function will be examinedcytologically and morphologically; and (2) to investigate the in vivo effect of OPN on woundhealing in experimental animal by histological, immunohistochemical and conventionalelectron microscopic techniques, and (3) to investigated the in vitro and in vivo effects ofOPN on the cancer cells (K7M2-WT and OPN-down regulated K7M2-shOPN cell lines) byculture system and transfering the cancer to null mice, respectively. We hope that after thecompletion of this project, we can understand more about functional roles of OPN in vivoand in vitro, and shed some light on the potential of using OPN as a therapeutic drug inaccelerating the wound healing and in treatment of cancer.骨調素細胞增生細胞移行細胞死亡血管新生傷口癒合癌化細胞癌轉移osteopontin (OPN)cell proliferationcell migrationcell deathangiogenesiswound healingcancer cellmetastasis