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Isolation of Cancer Stem-like Cells from Human Renal Cell Carcinoma Cell Line and Preliminary Study of Their Immune Escape Mechanisms

Author: ZhongYong
Tutor: ZhangShuRen;ZhangYouHui;LiuBinLei
School: Beijing Union Medical College
Course: Immunology
Keywords: Kidney Cancer Tumors ball Cancer stem cells Immune escape Regulatory T cells Suppressor cells of the myeloid sources
CLC: R737.11
Type: PhD thesis
Year: 2011
Downloads: 145
Quote: 0
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Abstract


Kidney cancer accounts for about 3.5% of all malignant tumors, it is also one of the most common tumors of the genitourinary system. Renal cell carcinoma is the most common malignant renal tumors, and its incidence is rising in the past 30 years. High degree of resistance embedded in metastatic renal cell carcinoma for radiotherapy and chemotherapy, approximately one-third of patients with renal cell metastasis in the initial diagnosis, while about 30-40% of patients in the surgical removal of the primary tumor within five years after distant metastasis, and poor clinical prognosis of renal cell carcinoma. Have been reported in the literature that the existence of cancer stem cells in a variety of hematological malignancies and solid tumors. And similar to normal stem cells, cancer stem cells have the ability to renew themselves, but it also has the potential of initiating and maintaining tumor growth. Cancer stem cells can not be the traditional means of anti-cancer completely clear, they may be the source of local recurrence and distant metastasis. Few reports so far about human renal cancer stem cell separation and identification. Beginning in the 1990s, before the emergence of the tyrosine kinase inhibitor, IFN-α and IL-2 immunotherapy is the standard formulation for the treatment of metastatic renal cell carcinoma. However, IFN-α and IL-2 immunotherapy inefficient, has been hovering in the 5-20% tumor immune escape may be one of the main factors affecting efficacy. Explore the the kidney cancer stem cell-mediated immune escape of great significance. In this study, we try vitro serum-free limited medium enriched human renal carcinoma cell line SK-RC-42 stem cells and explore its biological characteristics and its mediated immune escape mechanism. We found that the nerve sphere-like tumors ball SK-RC-42 adherent cells form in the limited medium. The tumor ball repeatedly passaged in vitro self-renewal capacity. Inoculation of tumor ball to serum-containing medium, adherent growth, differentiation potential. Tumors ball in the side population cell content of adherent cells was significantly higher. Tumors ball higher level expression of stem cell-associated genes: Oct3 / 4, Bmi-1, Nanog, β-catenin. Furthermore, tumor ball vitro height tolerate chemotherapy drugs and radiation treatment, has strong tumorigenicity in immunodeficient mice. Tumors ball and growth of adherent cells high level expression of stem cell related molecules: CD44, CD24 and CD105, CD133, CD34 almost no expression. Tumor ball high levels of expression of HLA-I molecules, and HLA-DR and costimulatory molecules CD80, CD86 almost no expression; the surface FAS and FASL molecules tumors ball expression were significantly lower than the growth of adherent cells; the tumors ball about 10% expression of B7-H1; almost all tumors ball high levels of expression the film complement regulatory proteins as well as FoxP3; tumors ball tumor-associated antigens hTERT expression and HER2 molecular significantly down. Function tests showed tumors ball significantly induced normal human T cell apoptosis, inhibition of cell generation induced regulatory T cells and myeloid origin. This study showed that tumor the ball culture can be enriched in human renal carcinoma cell line SK-RC-42 tumor stem cells SK-RC-42 renal cell carcinoma tumors ball may escape the attack of the immune system through a variety of channels. Explore their cell biological characteristics, and immune escape mechanism further expected to provide new ideas for the treatment of kidney cancer.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Urinary tumors > Kidney,renal pelvis tumor
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