The Functional Plasticity of Tumor Associated Macrophages in Ovarian Cancer cells Co-culture Assay and a Novel Ovarian Cancer Zebrafish Model

• Main Author: 陳婉馨
• Other Authors: 莊永仁
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/31838670896884573607

碩士 === 國立清華大學 === 生物資訊與結構生物研究所 === 100 === In Taiwan, ovarian cancer has the highest rate of mortality among all gynecological cancers. The high death rate is mostly due to the common absence or subtle symptom of ovarian cancer, which makes early detection a very challenging task. As a result, the metastatic spread of ovarian cancer becomes predominant and lead to poor prognosis. Among the variety of factors known to promote tumorigenesis and metastasis, macrophages infiltration is reported link to advanced ovarian cancer. Thus, to understand the ovarian cancer cells-macrophages interactions is necessary before one can develop new diagnostic and therapeutic strategies. Macrophages are the major components of inflammatory cells in ovarian cancer tissue. In general, macrophages can be classified into M1 and M2 phenotypes. M1 macrophages are immune-stimulating cells, while the M2 macrophages show tumor promotion properties and are also known as tumor-associated macrophages (TAMs). TAMs are shown to promote tumor growth, angiogenesis and metastasis of tumors. Many of the functions are mediated by cathepsins (CTSS). CTSS is a member of cysteine protease family. It is known that CTSS involve in tumor malignant transition, and the expression levels of CTSS are elevated in many tumor microenvironments in the presence of TAMs. In this study, we found both of M1 and M2 polarized macrophages stimulate CTSS expression in ovarian cancer cells, SKOV3 cells after co-culture. The result suggested these macrophages may change to be tumor-progression phenotype in the presence of ovarian cancer cells. Therefore, in this study, our first aim is to investigate the phenotypic switch of macrophages influenced by ovarian cancer cells via in vitro co-culture assays. Although cell co-culture assay provide a maneuverable system to study macrophage-cancer cell interactions, it cannot reflect the complex process of cancer development in the animal model system. To further investigate the ovarian carcinogenesis and the complex interplay between TAMs and ovarian cancer cells in vivo, we also aim to develop a novel ovarian cancer zebrafish model to take advantage of this aquatic vertebrate model organism’s low-cost and transparent features. We expect this zebrafish model could become a powerful tool to study pathological and biological features during ovarian cancer progression and metastasis.