IL-17在结直肠癌的表达和临床意义及其与SW480细胞的相互作用
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摘要
第一部分
目的
检测IL-17与STAT3在结直肠癌患者组织和外周血中的表达,探讨其与结直肠癌患者临床病理特征和肿瘤血管生成的关系。
方法
1.采用免疫组织化学SP法检测94例结直肠癌组织和31例正常肠黏膜组织中IL-17、STAT3蛋白的表达,并用CD34标记微血管计算微血管密度(MVD)。
2.收集7例结直肠癌患者和6例健康志愿者外周血标本,RT-PCR法检测外周血单个核细胞(PBMC)中IL-17 mRNA的表达。
3. ELISA法检测结直肠癌患者和健康人外周血血浆中IL-17蛋白的含量。
结果
1.免疫组织化学结果显示IL-17主要表达在结直肠癌组织中的肿瘤细胞和间质淋巴细胞胞浆内。IL-17在肿瘤细胞的阳性表达率和在间质淋巴细胞阳性表达数均明显高于其在正常肠黏膜的表达(P<0.01)；IL-17的表达与结直肠癌分化程度和Duke's分期有关(P<0.05)。STAT3在结直肠癌组织中的表达率显著高于其在正常肠黏膜中的表达(P<0.01),且与肿瘤细胞的分化程度、淋巴结转移和Duke's分期有关(P<0.05)。IL-17和STAT3在结直肠癌组织中的表达与MVD均有关(P<0.01)。Spearman等级相关分析表明IL-17和STAT3在结直肠癌组织中的表达呈正相关(r=0.282,P=0.006)。
2. RT-PCR结果显示结直肠癌患者PBMC中IL-17 mRNA表达水平明显高于健康对照组(P<0.01)。
3. ELISA结果显示结直肠癌患者外周血血浆中IL-17蛋白含量高于健康对照组(P<0.05)。
结论
1.IL-17在结直肠癌组织间质淋巴细胞中表达增加,并且结直肠癌Duke's分期越高、肿瘤细胞分化程度越低和MVD值越高,IL-17阳性淋巴细胞数量越多,提示IL-17可能来源于间质淋巴细胞,在结直肠癌的血管生成和生长转移过程中可能发挥促进作用。
2.IL-17与STAT3在结直肠癌组织的肿瘤细胞中高表达,并与MVD均有关,提示两者可能在结直肠癌的血管生成和肿瘤的发生发展中起到重要的协同作用。
3. IL-17 mRNA和蛋白在结直肠癌患者外周血表达上调,提示IL-17可能在结直肠癌的发生过程中起到了重要的调控作用。
第二部分
目的
探讨人结肠癌细胞株SW480对健康人PBMC产生IL-17的影响,并观察不同浓度的人重组白细胞介素17 (rhIL-17)对SW480细胞增殖、侵袭和迁移能力的影响。
方法
1.体外共培养SW480细胞和健康人PBMC, ELISA法检测不同时间段培养的PBMC上清液中IL-17蛋白的含量。
2.体外培养人结肠癌细胞株SW480,用不同浓度的rhIL-17处理细胞,MTT法检测细胞的生长变化。
3. Boyden小室法检测不同浓度的rhIL-17处理的SW480细胞侵袭、迁移能力的改变。
结果
1.SW480细胞处理组中PBMC的IL-17蛋白的含量明显增加,与自发培养组和刺激培养组相比差异具有统计学意义(P<0.05)。
2.SW480细胞经不同浓度的rhIL-17处理后,细胞增殖能力没有明显改变。
3.rhIL-17以剂量依赖的方式增强SW480细胞的侵袭和迁移能力,与正常对照组相比差异具有统计学意义(P<0.05)。
结论
1.SW480细胞可能促进PBMC产生内源性IL-17。
2.IL-17可能参与了SW480细胞的侵袭、迁移过程。
Part One
Objectives
To explore the relationship between the expression of IL-17 and STAT3 in blood and tissue of CRC, and to investigate their possible relationships with the clinic pathological features and the angiogenesis.
Methods
1. Immunohistochemistry (SP method) was used to detect the expression of IL-17 and STAT3 proteins in 94 specimens of colorectal carcinoma tissues and 31 cases normal mucosa membrane. Microvessel density (MVD) was counted based on CD34 marked endothelial cells of nicrovessels.
2. RT-PCR was used to detect the expression level of IL-17 mRNA in peripheral blood mononuclear cell (PBMC) of 7 colorectal carcinoma patients and 6 health people.
3. ELISA was used to detect the expression level of IL-17 protein in plasma of 7 colorectal carcinoma patients and 6 health people.
Results
1. Immunohistochemical data showed that IL-17 protein significantly expressed in cytoplasm of tumor cells and stromal lymphocytes of CRC tissues. The positive expressions of IL-17 in tumor cells and stroma lymphocytes were significantly higher than in normal mucous membrane (P<0.01). The expression of IL-17 was related to cancer cell differentiation and Duke's stage (P<0.05). Compared with corresponding normal tissues, the levels of STAT3 were significantly increased in tumors of CRC patients (P<0.01). The expression of STAT3 in CRC was related to cancer cell differentiation, metastasis of lymphnode and Duke's stage (P<0.05). MVD was closely correlated to the expression of IL-17 and STAT3 (P<0.01). and there was a stable positive relationship among the two proteins (r=0.282,P=0.006).
2. The expression level of IL-17 mRNA in patients" PBMC was higher than control group (P<0.01).
3. The expression level of IL-17 protein in patients' plasma was higher than control group (P<0.05).
Conclusion
1. The expression of IL-17 is up-regulated in stromal lymphocytes of CRC tissues, and the prevalence of intratumoral IL-17-producing cells correlate with the poorer differentiation and the higher Duke's stage. Moreover, the level of IL-17-producing cells are positively correlated the intratumoral MVD in tumor. It is suggested that IL-17 is derived from stromal lymphocytes in tumor. IL-17 may play an important role in the angiogenesis and metastasis of CRC.
2. IL-17 and STAT3 expressing are significantly higher in CRC tissues, and MVD is closely correlated to these factors. It is suggested that the two factors may play an important synergism role in the angiogenesis and carcinogenesis of CRC.
2. The expression level of IL-17 mRNA and protein are up-regulated in peripheral blood of CRC patients. It is implied that IL-17 is probably play an important regulation role involved in the pathogenesis of CRC.
Part Two
Objectives
To investigate the influence of human colon carcinoma cell line SW480 on IL-17 secreted by PBMC of healthy people in vitro and to examine the effect of recombinant human IL-17 (rhIL-17) on the proliferation, invasion and motility of SW480.
Methods
1. ELISA was used to detect the expression level of IL-17 protein in supernatants of PBMC cocultured with SW480 in vitro.
2. Human colon carcinoma cell line SW480 cultured were treated respectively with different concentrations of rhIL-17. The effects of rhIL-17 on the proliferation property of SW480 were detected by MTT colorimetric assay.
2. Boyden chamber were used to detect the effects of rhIL-17 with different concentrations on the invasion and motility of SW480.
Results
1. IL-17 levels in supernatants from SW480 cocultures were higher than that of in medium alone and OKT3-preactivated PBMC (P<0.01).
2. Human colon carcinoma cell line SW480 cultured in vitro were treated respectively with different concentrations of rhIL-17. The effects of rhlL-17 on the proliferation property of SW480 were detected by MTT colorimetric assay.
3. Boyden chamber were used to detect the effects of rhIL-17 with different concentrations on the invasion and motility of SW480.
Conclusion
1. Tumor cells may facilitate the generation of IL-17 by PBMC.
2. IL-17 may regulate the invasion and motility of the SW480 cells.
目的
检测IL-17与STAT3在结直肠癌患者组织和外周血中的表达,探讨其与结直肠癌患者临床病理特征和肿瘤血管生成的关系。
方法
1.采用免疫组织化学SP法检测94例结直肠癌组织和31例正常肠黏膜组织中IL-17、STAT3蛋白的表达,并用CD34标记微血管计算微血管密度(MVD)。
2.收集7例结直肠癌患者和6例健康志愿者外周血标本,RT-PCR法检测外周血单个核细胞(PBMC)中IL-17 mRNA的表达。
3. ELISA法检测结直肠癌患者和健康人外周血血浆中IL-17蛋白的含量。
结果
1.免疫组织化学结果显示IL-17主要表达在结直肠癌组织中的肿瘤细胞和间质淋巴细胞胞浆内。IL-17在肿瘤细胞的阳性表达率和在间质淋巴细胞阳性表达数均明显高于其在正常肠黏膜的表达(P<0.01)；IL-17的表达与结直肠癌分化程度和Duke's分期有关(P<0.05)。STAT3在结直肠癌组织中的表达率显著高于其在正常肠黏膜中的表达(P<0.01),且与肿瘤细胞的分化程度、淋巴结转移和Duke's分期有关(P<0.05)。IL-17和STAT3在结直肠癌组织中的表达与MVD均有关(P<0.01)。Spearman等级相关分析表明IL-17和STAT3在结直肠癌组织中的表达呈正相关(r=0.282,P=0.006)。
2. RT-PCR结果显示结直肠癌患者PBMC中IL-17 mRNA表达水平明显高于健康对照组(P<0.01)。
3. ELISA结果显示结直肠癌患者外周血血浆中IL-17蛋白含量高于健康对照组(P<0.05)。
结论
1.IL-17在结直肠癌组织间质淋巴细胞中表达增加,并且结直肠癌Duke's分期越高、肿瘤细胞分化程度越低和MVD值越高,IL-17阳性淋巴细胞数量越多,提示IL-17可能来源于间质淋巴细胞,在结直肠癌的血管生成和生长转移过程中可能发挥促进作用。
2.IL-17与STAT3在结直肠癌组织的肿瘤细胞中高表达,并与MVD均有关,提示两者可能在结直肠癌的血管生成和肿瘤的发生发展中起到重要的协同作用。
3. IL-17 mRNA和蛋白在结直肠癌患者外周血表达上调,提示IL-17可能在结直肠癌的发生过程中起到了重要的调控作用。
第二部分
目的
探讨人结肠癌细胞株SW480对健康人PBMC产生IL-17的影响,并观察不同浓度的人重组白细胞介素17 (rhIL-17)对SW480细胞增殖、侵袭和迁移能力的影响。
方法
1.体外共培养SW480细胞和健康人PBMC, ELISA法检测不同时间段培养的PBMC上清液中IL-17蛋白的含量。
2.体外培养人结肠癌细胞株SW480,用不同浓度的rhIL-17处理细胞,MTT法检测细胞的生长变化。
3. Boyden小室法检测不同浓度的rhIL-17处理的SW480细胞侵袭、迁移能力的改变。
结果
1.SW480细胞处理组中PBMC的IL-17蛋白的含量明显增加,与自发培养组和刺激培养组相比差异具有统计学意义(P<0.05)。
2.SW480细胞经不同浓度的rhIL-17处理后,细胞增殖能力没有明显改变。
3.rhIL-17以剂量依赖的方式增强SW480细胞的侵袭和迁移能力,与正常对照组相比差异具有统计学意义(P<0.05)。
结论
1.SW480细胞可能促进PBMC产生内源性IL-17。
2.IL-17可能参与了SW480细胞的侵袭、迁移过程。
Part One
Objectives
To explore the relationship between the expression of IL-17 and STAT3 in blood and tissue of CRC, and to investigate their possible relationships with the clinic pathological features and the angiogenesis.
Methods
1. Immunohistochemistry (SP method) was used to detect the expression of IL-17 and STAT3 proteins in 94 specimens of colorectal carcinoma tissues and 31 cases normal mucosa membrane. Microvessel density (MVD) was counted based on CD34 marked endothelial cells of nicrovessels.
2. RT-PCR was used to detect the expression level of IL-17 mRNA in peripheral blood mononuclear cell (PBMC) of 7 colorectal carcinoma patients and 6 health people.
3. ELISA was used to detect the expression level of IL-17 protein in plasma of 7 colorectal carcinoma patients and 6 health people.
Results
1. Immunohistochemical data showed that IL-17 protein significantly expressed in cytoplasm of tumor cells and stromal lymphocytes of CRC tissues. The positive expressions of IL-17 in tumor cells and stroma lymphocytes were significantly higher than in normal mucous membrane (P<0.01). The expression of IL-17 was related to cancer cell differentiation and Duke's stage (P<0.05). Compared with corresponding normal tissues, the levels of STAT3 were significantly increased in tumors of CRC patients (P<0.01). The expression of STAT3 in CRC was related to cancer cell differentiation, metastasis of lymphnode and Duke's stage (P<0.05). MVD was closely correlated to the expression of IL-17 and STAT3 (P<0.01). and there was a stable positive relationship among the two proteins (r=0.282,P=0.006).
2. The expression level of IL-17 mRNA in patients" PBMC was higher than control group (P<0.01).
3. The expression level of IL-17 protein in patients' plasma was higher than control group (P<0.05).
Conclusion
1. The expression of IL-17 is up-regulated in stromal lymphocytes of CRC tissues, and the prevalence of intratumoral IL-17-producing cells correlate with the poorer differentiation and the higher Duke's stage. Moreover, the level of IL-17-producing cells are positively correlated the intratumoral MVD in tumor. It is suggested that IL-17 is derived from stromal lymphocytes in tumor. IL-17 may play an important role in the angiogenesis and metastasis of CRC.
2. IL-17 and STAT3 expressing are significantly higher in CRC tissues, and MVD is closely correlated to these factors. It is suggested that the two factors may play an important synergism role in the angiogenesis and carcinogenesis of CRC.
2. The expression level of IL-17 mRNA and protein are up-regulated in peripheral blood of CRC patients. It is implied that IL-17 is probably play an important regulation role involved in the pathogenesis of CRC.
Part Two
Objectives
To investigate the influence of human colon carcinoma cell line SW480 on IL-17 secreted by PBMC of healthy people in vitro and to examine the effect of recombinant human IL-17 (rhIL-17) on the proliferation, invasion and motility of SW480.
Methods
1. ELISA was used to detect the expression level of IL-17 protein in supernatants of PBMC cocultured with SW480 in vitro.
2. Human colon carcinoma cell line SW480 cultured were treated respectively with different concentrations of rhIL-17. The effects of rhIL-17 on the proliferation property of SW480 were detected by MTT colorimetric assay.
2. Boyden chamber were used to detect the effects of rhIL-17 with different concentrations on the invasion and motility of SW480.
Results
1. IL-17 levels in supernatants from SW480 cocultures were higher than that of in medium alone and OKT3-preactivated PBMC (P<0.01).
2. Human colon carcinoma cell line SW480 cultured in vitro were treated respectively with different concentrations of rhIL-17. The effects of rhlL-17 on the proliferation property of SW480 were detected by MTT colorimetric assay.
3. Boyden chamber were used to detect the effects of rhIL-17 with different concentrations on the invasion and motility of SW480.
Conclusion
1. Tumor cells may facilitate the generation of IL-17 by PBMC.
2. IL-17 may regulate the invasion and motility of the SW480 cells.
引文
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[1]Zhang B, Rong G, Wei H, et al. The prevalence of Th17 cells in patients with gastric cancer [J]. Biochem Biophys Res Commun,2008,374 (3):533-537.
[2]Miyahara Y, Odunsi K, Chen W, et al. Generation and regulation of human CD4'IL-17-producing T cells in ovarian cancer [J]. Proc Natl Acad Sci, USA,2008,105 (40):15505-15510.
[3]Dhodapkar KM, Barhuto S, Matthews P, et al. Dendritic cells mediate the induction of polyfunctional human IL17-Producing cells(Th17-1cells) enriehed in the bone marrow of patients with myeloma [J]. Blood,2008,112 (7):2878-2885.
[4]Zhang JP, Yan J, Xu J, et al. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients [J]. J Hepatol,2009,50 (5):980-989.
[5]Nam JS, Terabe M, Kang MJ, et al. Transforming growth factor-β subverts the immune system into directly promoting tumor growth through interleukin-17 [J]. Cancer Res,2008. 68(10):3915-3923.
[6]Kortylewski M, Xin H, Kujawski M, et al. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment [J]. Cancer Cell,2009,15 (2):114-123.
[7]Chizzolini C, Chicheportiche R, Alvarez M, et al. Prostagland in E2 synergistically with interleukin-23 favors human Th17 expansion [J]. Blood,2008,112(9):3696-3703.
[8]Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics [J]. CA Cancer J Clin,2005,55 (2):74-108.
[9]Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites [J]. Nat Rev Cancer,2002,2 (8):563-572.
[10]Mehlen P, Puisieux A. Metastasis:a question of life or death [J]. Nat Rev Cancer,2006,6 (6):449-458.
[11]Gupta GP, Massague J. Cancer metastasis:building a framework [J]. Cell,2006,127 (4): 679-695.
[12]Witowski J, Ksiazek K, Jorres A:Interleukin-17:a mediator of inflammatory responses [J]. Cell Mol Life Sci,2004.61 (5):567-579.
[13]Murugaiyan G, Saha B. Protumor vs antitumor functions of IL-17 [J]. Immunol,2009,183 (7):4169-4175.
[14]He D, Li H, Yusuf N, et al. IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells [J]. J. Immunol.2010.184(5):2281-2288.
[15]Hirahara N, Nio Y, Sasaki S, et al. Inoculation of human interleukin-17 gene-transfected Meth-A fibrosarcoma cells induces T cell-dependent tumor specific immunity in mice [J]. Oncology,2001,61 (1):79-89.
[16]Inozume T, Hanada K, Wang QJ, et al. IL-17 secreted by tumor reactive T cells induces IL-8 release by human renal cancer cells [J]. J. Immunother,2009,32 (2):109-117.
[17]Tartour E. Fossiez F, Joyeux I, et al. Interleukin 17. a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumor s in nude mice [J]. Cancer Res,1999,59 (15):3698 -3704.
[18]Numasaki M, Watanabe M, Suzuki T, et al. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis [J]. J Immunol,2005,175 (9):6177-6189.
[19]Honorati MC, Neri S, Cattini L et al. Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts [J]. Osteoarthritis Cartilage,2006,14 (4):345-352.
[20]Takahashi H, Numasaki M, Lotze MT, and Sasaki H. Interleukin-17 enhances bFGF-, HGF-and VEGF-induced growth of vascular endothelial cells [J]. Immunol Lett,2005,98 (2):189-193.
[21]Jeon SH, Chae BC, Kim HA, et al. Mechanisms underlying TGF-β1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis [J]. Leukocyte Biol,2007,81 (2):557-566.
[22]Huang X, and Lee C. Regulation of stromal proliferation, growth arrest, differentiation and apoptosis in benign prostatic hyperplasia by TGF-β [J]. Front. Biosci,2003,8:s740-s749.
[23]Numasaki M, Lotze MT, and Sasaki H. Interleukin-17 augments tumor necrosis factor-a-induced elaboration of proangiogenic factors from fibroblasts [J]. Immunol Lett, 2004,93(1):39-43.
[24]Wang L, Yi T, Kortylewski M, et al. IL-17 can promote tumor growth through an IL-6-STAT3 signaling pathway y[J]. J Exp Med,2009,206 (7):1457-1464.
[25]Kehlen A, Thiele K, Riemann D, et al. Interleukin-17 stimulates the expression of IκBα mRNA and the secretion of IL-6 and IL-8 in glioblastoma cell lines [J]. Neuroimmunol,1999, 101 (1):1-6.
[26]Kryczek I, Banerjee M, Cheng P, et al. Phenotype, distribution, generation, functional and clinical relevance of Th17 cells in the human tumor environments [J]. Blood,2009,114 (6): 1141-1149.
[27]Pongcharoen S, Niumsup P, Sanguansermsri D, et al. The effect of interleukin-17 on the proliferation and invasion of JEG -3 human choriocarcinoma cells [J]. Am J Reprod Immunol,2006,55 (4):291-300.
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[31]Tanaka J, Watanabe N, Kido M, et al. Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2-polarizing conditions [J]. Clin Exp Allergy,2009,39 (1):89-100.
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[1]Zhang B, Rong G, Wei H, et al. The prevalence of Th17 cells in patients with gastric cancer [J]. Biochem Biophys Res Commun,2008,374 (3):533-537.
[2]Miyahara Y, Odunsi K, Chen W, et al. Generation and regulation of human CD4'IL-17-producing T cells in ovarian cancer [J]. Proc Natl Acad Sci, USA,2008,105 (40):15505-15510.
[3]Dhodapkar KM, Barhuto S, Matthews P, et al. Dendritic cells mediate the induction of polyfunctional human IL17-Producing cells(Th17-1cells) enriehed in the bone marrow of patients with myeloma [J]. Blood,2008,112 (7):2878-2885.
[4]Zhang JP, Yan J, Xu J, et al. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients [J]. J Hepatol,2009,50 (5):980-989.
[5]Nam JS, Terabe M, Kang MJ, et al. Transforming growth factor-β subverts the immune system into directly promoting tumor growth through interleukin-17 [J]. Cancer Res,2008. 68(10):3915-3923.
[6]Kortylewski M, Xin H, Kujawski M, et al. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment [J]. Cancer Cell,2009,15 (2):114-123.
[7]Chizzolini C, Chicheportiche R, Alvarez M, et al. Prostagland in E2 synergistically with interleukin-23 favors human Th17 expansion [J]. Blood,2008,112(9):3696-3703.
[8]Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics [J]. CA Cancer J Clin,2005,55 (2):74-108.
[9]Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites [J]. Nat Rev Cancer,2002,2 (8):563-572.
[10]Mehlen P, Puisieux A. Metastasis:a question of life or death [J]. Nat Rev Cancer,2006,6 (6):449-458.
[11]Gupta GP, Massague J. Cancer metastasis:building a framework [J]. Cell,2006,127 (4): 679-695.
[12]Witowski J, Ksiazek K, Jorres A:Interleukin-17:a mediator of inflammatory responses [J]. Cell Mol Life Sci,2004.61 (5):567-579.
[13]Murugaiyan G, Saha B. Protumor vs antitumor functions of IL-17 [J]. Immunol,2009,183 (7):4169-4175.
[14]He D, Li H, Yusuf N, et al. IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells [J]. J. Immunol.2010.184(5):2281-2288.
[15]Hirahara N, Nio Y, Sasaki S, et al. Inoculation of human interleukin-17 gene-transfected Meth-A fibrosarcoma cells induces T cell-dependent tumor specific immunity in mice [J]. Oncology,2001,61 (1):79-89.
[16]Inozume T, Hanada K, Wang QJ, et al. IL-17 secreted by tumor reactive T cells induces IL-8 release by human renal cancer cells [J]. J. Immunother,2009,32 (2):109-117.
[17]Tartour E. Fossiez F, Joyeux I, et al. Interleukin 17. a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumor s in nude mice [J]. Cancer Res,1999,59 (15):3698 -3704.
[18]Numasaki M, Watanabe M, Suzuki T, et al. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis [J]. J Immunol,2005,175 (9):6177-6189.
[19]Honorati MC, Neri S, Cattini L et al. Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts [J]. Osteoarthritis Cartilage,2006,14 (4):345-352.
[20]Takahashi H, Numasaki M, Lotze MT, and Sasaki H. Interleukin-17 enhances bFGF-, HGF-and VEGF-induced growth of vascular endothelial cells [J]. Immunol Lett,2005,98 (2):189-193.
[21]Jeon SH, Chae BC, Kim HA, et al. Mechanisms underlying TGF-β1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis [J]. Leukocyte Biol,2007,81 (2):557-566.
[22]Huang X, and Lee C. Regulation of stromal proliferation, growth arrest, differentiation and apoptosis in benign prostatic hyperplasia by TGF-β [J]. Front. Biosci,2003,8:s740-s749.
[23]Numasaki M, Lotze MT, and Sasaki H. Interleukin-17 augments tumor necrosis factor-a-induced elaboration of proangiogenic factors from fibroblasts [J]. Immunol Lett, 2004,93(1):39-43.
[24]Wang L, Yi T, Kortylewski M, et al. IL-17 can promote tumor growth through an IL-6-STAT3 signaling pathway y[J]. J Exp Med,2009,206 (7):1457-1464.
[25]Kehlen A, Thiele K, Riemann D, et al. Interleukin-17 stimulates the expression of IκBα mRNA and the secretion of IL-6 and IL-8 in glioblastoma cell lines [J]. Neuroimmunol,1999, 101 (1):1-6.
[26]Kryczek I, Banerjee M, Cheng P, et al. Phenotype, distribution, generation, functional and clinical relevance of Th17 cells in the human tumor environments [J]. Blood,2009,114 (6): 1141-1149.
[27]Pongcharoen S, Niumsup P, Sanguansermsri D, et al. The effect of interleukin-17 on the proliferation and invasion of JEG -3 human choriocarcinoma cells [J]. Am J Reprod Immunol,2006,55 (4):291-300.
[28]Su X, Ye J, Hsueh EC, et al. Tumor microenvironments direct the recruitment and expansion of human Th17 cells [J]. J Immunol,2010,184 (3):1630-1641.
[29]Van B, Zelinkova Z, Taanman K, et al. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells [J]. Immunity,2007,27 (4):660-669.
[30]Evans HG, Suddaso T, Jackson I, et al. Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes [J]. Proc Nati Acad Sci USA,2007,104 (43):17034-17039.
[31]Tanaka J, Watanabe N, Kido M, et al. Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2-polarizing conditions [J]. Clin Exp Allergy,2009,39 (1):89-100.
[32]Kryczek I, Wei S. Szeliga W, et al. Endogenous IL-17 contributes to reduced tumor growth and metastasis [J]. Blood,2009,114 (2):357-359.
[33]Benchetrit F, Ciree A, Vives V, et al. Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism [J]. Blood,2002,99 (6):2114-2121.
[34]Zhu XW. Mulcahy LA, Mohammed RA, el al. IL-17 expression by breast-cancer-associated macrophages:IL-17 promotes invasiveness of breast cancer cell lines [J]. Breast Cancer Res, 2008,10(6):R95.
[35]Fossiez F, Djossou O, Chornarat P, et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J]. J Exp Med,1996,183 (6):2593-2603.
[36]Waugh DJ, Wilson C. The interleukin-8 pathway in cancer [J]. Clin Cancer Res,2008,14 (21):6735-6741.