跳到主要內容

臺灣博碩士論文加值系統

(18.97.14.87) 您好!臺灣時間:2025/02/09 10:45
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:呂盈璋
研究生(外文):Ying-Chang Lu
論文名稱:間質細胞衍生因子及其受體在人類喉癌和下咽癌細胞移行/侵襲能力上所扮演的角色
論文名稱(外文):The Role of SDF-1/CXCR4 on Human Laryngeal and Hypopharyngeal Cancer Cells Migration/Invasion Capability
指導教授:郭明良郭明良引用關係
指導教授(外文):Min-Liang Kuo
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:毒理學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:78
中文關鍵詞:間質細胞衍生因子咽喉鱗狀上皮細胞癌
外文關鍵詞:SDF-1LHSCC
相關次數:
  • 被引用被引用:0
  • 點閱點閱:319
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
喉癌及下咽癌(統稱咽喉癌)是常見的頭頸部癌症之一,它的組織病理學診斷百分之九十以上為鱗狀上皮細胞癌,雖然醫學逐漸進步,但此疾病患者的存活率在最近20年內並沒有增加的現象,對咽喉癌病患的治療而言,是否出現淋巴結及遠隔轉移對預後具有決定性的影響。眾所週知,癌症的轉移並非隨意發生的過程,不同的癌症會轉移到不同的部位,雖然有許多因子已知可能與癌症的轉移有關,但真正決定癌症細胞移動的方向,以及侵入特殊器官的機轉仍未被釐清。近年的研究顯示化學激活素(chemokine) CXC受體第4號( CXCR4 )及其配體間質細胞衍生因子第1號(SDF-1/ CXCL12),在某些實體腫瘤的轉移中扮演重要的角色,然而此一路徑在咽喉癌轉移的重要性仍不清楚。因此本計畫即在探討CXCL12/ CXCR4在咽喉癌的轉移中可能扮演的角色。
從免疫組織化學與反轉錄聚合酶連鎖反應結果顯示,由咽喉癌病患所採集的原位腫瘤組織中其CXCR4具有高度表現的現象。在咽喉癌細胞株中,利用反轉錄聚合酶連鎖反應與西方墨點法可分別觀察到CXCR4 mRNA與其蛋白質高度表現的情形,同時免疫組織化學法可於細胞表面偵測到CXCR4的表現。在本實驗中,我們證實CXCL12能促進細胞的化學趨化與侵襲的能力,而此特性可被CXCR4拮抗劑JM3100所阻斷。同時,我們研究能調節與CXCL12/ CXCR4此一路徑所誘發之咽喉癌細胞對細胞外基質進行細胞移行與侵襲的訊息傳遞機轉。由實驗結果得知,CXCL12所誘發活化的MMP-13能增加咽喉癌細胞的化學侵襲性,並且是透過活化AP-1與細胞外訊息調節激酶(ERK1/2)所完成。專一性的ERK1/2抑制劑(U0126)阻斷ERK1/2訊息傳遞分子則可有效抑制MMP-13的表現及減少LHSCC細胞的侵襲性。c-Jun antisense oligodeoxynucleotide (ODN)可有效抑制MMP-13的表現,但sense之ODN則無此反應。綜合上述結果,我們證實CXCL12/ CXCR4所誘發之咽喉癌細胞的趨化侵襲性與ERK1/2、AP-1與MMP-13活化有關,而此一路徑可能在咽喉癌的轉移上扮演著重要的角色。綜合以上實驗結果可使吾人更加了解咽喉癌轉移的機轉,而藉由對此一機制的進一步探討可能可以尋求新的輔助療法,以嘗試減少轉移,改善病人的存活率。
Cancer of the larynx and hypopharynx is one of the most common head and neck malignancy. Squamous cell carcinoma remains the most common pathologic type, accounting for more than 90% cases. Although therapeutic modality has improved gradually, there is no sign that the 5-year survival rate has improved during the past 20 years. The metastasis of tumor cells represents the primary source of clinical morbidity and mortality in the large majority of laryngeal and hypopharyngeal tumors. Cancer metastasis is not a random process and different cancer types have different metastatic sites. Though there are a number of molecules that have been shown to play a role in the metastatic process, the exact mechanisms determining the directional migration and invasion of tumor cells into specific organs have not been clearly established . Recent research has demonstrated the possible role of chemokine receptor, CXCR4, and its ligand stromal cell-derived factor-1 (SDF-1/ CXCL12) in the metastasis of some solid tumors. However, the role of /CXCR4 in metastasis of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) is still unknown. Therefore, in this study we have investigated the role of CXCL12/ CXCR4 system in the metastasis of LHSCC. Immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) of primary tumor samples from LHSCC patients revealed high expression of CXCR4.RT-PCR and Western blot examination demonstrated CXCR4 mRNA and protein expression in LHSCC cell lines. Immunohistochemistry demonstrated CXCR4 surface expression. In the present study, we showed that CXCL12 enhanced the chemotaxis and chemoinvasion properties of cells, which could be blocked by CXCR4 antagonist (JM3100). We also examined the signaling mechanisms that regulate CXCL12-induced and CXCR4-mediated LHSCC cell motility and invasion to extracellular matrix. We found that CXCL12-induced MMP-13 activation which resulted in an increased chemoinvasion of LHSCC cells. This was mediated by extracellular signal-regulated kinase 1/2 activation. Blocking ERK1/2 pathway by specific ERK1,2 inhibitor U0126 resulted in suppression of MMP-13 expression and decreasing chemoinvasion of LHSCC cells. c-Jun antisense, but not sense, oligodeoxynucleotide (ODN ) also significantly decreases MMP-13 expression. We conclude that CXCL12/CXCR4-mediated chemotaxis and chemoinvasion is through activation of ERK1/2 AP-1 and MMP-13, and this pathway might play an important role in the metastasis of LHSCC. The results of this study will provide evidence for us to understand the mechanism of metastasis in laryngeal and hypopharyngeal SCC. Searching for a new therapeutic agent to block this pathway as an adjuvant therapy for laryngeal SCC, might reduce the metastasis rates and improve the survival rates.
一、誌謝 2
二、中文摘要 3
三、英文摘要 5
四、前言 8
五、實驗材料與方法 23
六、結果 35
七、討論 42
八、參考文獻 48
九、圖表 57
Aiuti A., Webb I.J., Bleul C, Springer T., and Gutierrez-Ramos J.C.:The chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J.Exp. Med. 185, No1, Jan.1, 111-120,1997
Alexander,C.M., Hansell,E.J., Behrendtsen,O., Flannery,M.L., Kishnani,N.S., Hawkes,S.P., and Werb,Z. (1996). Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation. Development - Supplement 122, 1723-1736.
Alho,A.M. and Underhill,C.B. (1989). The hyaluronate receptor is preferentially expressed on proliferating epithelial cells. Journal of Cell Biology 108, 1557- 1565.
Aljada A, Ghanim H, Mohanty P, Hofmeyer D, Tripathy D, Dandona P. Hydrocortisone suppresses intranuclear activator-protein-1 (AP-1) binding activity in mononuclear cells and plasma matrix metalloproteinase 2 and 9 (MMP- 2 and MMP-9). J. Clin. Endocrinol. Metab. 2001; 86:5988-91.
Baggiolini, M. Chemokines in pathology and medicine. J Intern Med,250:91-104, 2001
Bleul C.C, Fuhlbrigge R.C., Casasnovas J.M., Aiuti A., Spronger T.A.:A highly efficacious lymphocytr chemoattractant, stromal cell- derived factor 1 (SDF-1). J.Exp. Med. 184: 1101-1109, 1996
Bleul, C. C., Wu, L., Hoxie, J. A., Springer, T. A., and Mackay, C. R. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A, 94: 1925-1930, 1997.
Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989; 49: 4682-4689.
Burger, M., Glodek, A., Hartmann, T., Schmitt-Graff, A., Silberstein, L. E., Fujii, N., Kipps, T. J., and Burger, J. A. Functional expression of CXCR4 (CD184) on small-cell lung cancer cells mediates migration, integrin activation, and adhesion to stromal cells. Oncogene, 22: 8093-8101, 2003.
Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2: 563-572.
Conner EA, Teramoto T, Wirth PJ, Kiss A, Garfield S, Thorgeirsson SS. HGF-mediated apoptosis via p53/bax-independent pathway activating JNK1. Carcinogenesis 1999; 20: 583-590.
Deryugina, E. I., Bourdon, M. A., Luo, G. X., Reisfeld, R. A., and Strongin, A. Matrix metalloproteinase-2 activation modulates glioma cell migration (1997) J. Cell Sci. 110, 2473-2482
D. Uchida, N.M. Begum, A. Almofti, K. Nakashiro, H. Kawamata, Y. Tateishi, H. Hamakawa, H. Yoshida and M. Sato. Possible role of stromal-cell-derived factor-1/CXCR4 signaling on lymph node metastasis of oral squamous cell carcinoma Exp. Cell Res. 290 (2003), pp. 289–302.
Donzella G. A., Schols D., Lin S. W., Este J. A., Nagashima K. A., Maddon P. J., Allaway G. P., Sakmar T. P., Henson G., De Clercq E., Moore J. P. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat. Med., 4: 72-77, 1998.
F. Alves, U. Borchers, B. Padge, H. Augustin, K. Nebendahl, G. Kloppel and L.F. Tietze. Inhibitory effect of a matrix metalloproteinase inhibitor on growth and spread of human pancreatic ductal adenocarcinoma evaluated in an orthotopic severe combined immunodeficient (SCID) mouse model . Cancer Lett. 165 (2001), pp. 161–170.
Ganju R.K., Brubaker S.A., Meyer J., Dutt P., Yang Y., Qin S., Newman W., Groopman J.E.:The α-chemokine, stromal cell-derived factor-1α, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activated mutiple signal transduction pathways. The J. of Biol. Chem. 273, No6, Sept 4:23169-23175, 1998
Giatromanolaki A. Prognostic role of angiogenesis in non-small cell lung cancer. Anticancer Res. 2001; 21: 4373-4382.
Gupta, S. K., Lysko, P. G., Pillarisetti, K., Ohlstein, E., and Stadel, J. M. Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines. J Biol Chem, 273: 4282-4287, 1998.
Han Y., He T., Huang D., Pardo C. A., Ransohoff R. M. TNF-a mediates SDF-1a-induced NF-kB activation and cytotoxic effects in primary astrocytes. J. Clin. Investig., 108: 425-435, 2001.
Hendrix C. W., Flexner C., MacFarland R. T., Giandomenico C., Fuchs E. J., Redpath E., Bridger G., Henson G. W. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob. Agents Chemother., 44: 1667-1673, 2000.
Hesselgesser, J., Halks-Miller, M., DelVecchio, V., Peiper, S. C., Hoxie, J., Kolson, D. L., Taub, D., and Horuk, R. CD4-independent association between HIV-1 gp120 and CXCR4: functional chemokine receptors are expressed in human neurons. Curr Biol, 7: 112-121, 1997.
Inngjerdingen M., Torgersen K.M, Maghazachi A.A.:Lck is required for stromal cell- derived factor 1α (CXCL12)- induced lymphoid cell chemotaxis. Blood, 99, No.12, June 15: 4318-4325, 2002
J.A. Uria, M. Stahle-Backdahl, M. Seiki, A. Fueyo, C. Lopez-Otin, Regulation of collagenase-3 expression in human breast carcinomas is mediated by stromal-epithelial cell interactions, Cancer Res. 57 (1997) 4882-4888
Janowska-Wieczorek A, Marquez LA, Dobrowsky A, Ratajczak MZ, Cabuhat ML.: Differential MMP and TIMP production by human marrow and peripheral blood CD34(+) cells in response to chemokines. Exp Hematol. 2000 Nov;28(11):1274-85.
Johnsen M, Lund LR, Romer J, Almholt K, Dano K. Cancer invasion and tissue remodeling: common themes in proteolytic matrix degradation. Curr. Opin. Cell. Biol. 1998; 10:667-71.
Karin M., Liu Z.-G., Zandi E., AP-1 function and regulation. AP-1 function and regulation . Curr. Opin. Cell Biol., Volume: 9, (1997), pp. 240—246
Kim C.H., Broxymer H.E.:In vitro behavior of haematopoietic progenitor cells under the influence of chemoattractant, stromal cell- derived factor-1, steel factor, and bone marrow environment. Blood 91:100-110, 1998
Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS, Chung J. Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 2001; 15:1953-62.
Komori, H. Yagi, S. Nomua, A. Yamaguchi, K. Sasaki, K. Deguchi, Y. Shimizu, R. T. Bronson, Y.H. Gao, M.Inada, M.Sato, R. Okamoto, Y. Kitamura, S. Yoshiki, T. Kishimoto, Targeted disrubtion of Cbfal results in acomplete lack of bone formation owing to maturational arrest of osteoblasts, Cell 89(1997) 755-764
Koshiba, T., Hosotani, R., Miyamoto, Y., Ida, J., Tsuji, S., Nakajima, S., Kawaguchi, M., Kobayashi, H., Doi, R., Hori, T., Fujii, N., and Imamura, M. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression. Clin Cancer Res, 6: 3530-3535, 2000.
Kubiatowski T, Jang T, Lachyankar MB, Salmonsen R, Nabi RR, Quesenberry PJ, Litofsky NS, Ross AH, Recht LD. Association of increased phosphatidylinositol 3-kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas. J. Neurosurg. 2001; 95:480-8.
Lavi, E., J. M. Strizki, A. M. Ulrich, W. Zhang, L. Fu, Q. Wang, M. O''Connor, J. A. Hoxie, and F. Gonzalez-Scarano. 1997. CXCR-4 (fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1), is expressed in the human brain in a variety of cell types, including microglia and neurons. Am. J. Pathol. 151:1035-1041.
Liabakk NB, Talbot I, Smith RA, Wilkinson K, Balkwill F. Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res. 1996; 56:190-6.
Libura J, Drukala J, Majka M, Tomescu O, Navenot JM, Kucia M, Marquez L, Peiper SC, Barr FG, Janowska-Wieczorek A, Ratajczak MZ.: CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion. Blood. 2002 Oct 1;100(7):2597-606.
Madri, J., Graesser, D., and Haas, T. (1996) Biochem. Cell Biol. 74, 749-757
Ma Q., Jones D., Borghesani P.R., and Springer T.:Impaired B-lymphopoiesis , myelopoiesis, and derailed cerebellar neuron migration in CXCR4 and SDF-1- deficient mice. Proc. Natl. Acad Sci. USA 95:9448-9453, 1998
Mohle R., Bautz F., Rafii S., and Lothar K.:Regulation of transendothelial migration of hematopoietic progenitor cells. Annu NY Aca.of Science. 872: 176- 186, 1999
Muller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanghan, T., Murphy, E., Yuan, W., Wagner, S. N., Barrera, J. L., Mohar, A., Verastegui, E., and Zlotnik, A. Involvement of chemokine receptors in breast cancer metastasis (2001) Nature 410, 50-56
Murakami, T., Maki, W., Cardones, A. R., Fang, H., Tun Kyi, A., Nestle, F. O., and Hwang, S. T. Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Res, 62: 7328-7334, 2002.
Nagasawa T., Hirota S., Tachibana K., and Kishimoto T.:Defects of B-cell lymphopoiesis and bone marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382, August 15: 635-638, 1996
Nagasawa T., Nakajima T., Tachibaba K., Iizasa H., Bleul C. C., Yoshie O., Matsushima K., Yoshida N., Springer T. A., Kishimoto T. Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin. Proc. Natl. Acad. Sci. USA, 93: 14726-14729, 1996.
Okabe S., Fukuda S., Broxmeyer H.E.:Activation of Wiskott- Aldrich syndrome protein and its association with other proteins by stromal cell- derived factor-1α is associated with cell migration in a T-lymphocyte line. Exper. Hemat. 30: 761-766, 2002
Overall CM, Lopez-Otin C. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer 2002; 2: 657-672.
Palanki MS. Inhibitors of AP-1 and NF-kappa B mediated transcriptional activation: therapeutic potential in autoimmune diseases and structural diversity. Curr. Med. Chem. 2002; 9:219-27.
Pan MR, Hung WC. Nonsteroidal anti-inflammatory drugs inhibit matrixl metalloproteinase-2 via suppression of the ERK/Sp1-mediated transcription. J. Biol. Chem. 2002; 277:32775-80.
Park BK, Zeng X, Glazer RI. Akt1 induces extracellular matrix invasion and matrix metalloproteinase-2 activity in mouse mammary epithelial cells. Cancer Res. 2001; 61:7647-53.
Parks WC, and Mecham RP. Matrix metalloproteinases.1998 Academic Press. San Diego.
Peled A., Grabovsky V., Habler L., Sandbank J., Arenzana-Seisdedos F., Petir I., Ben-Hur H., Lapidot T.:The chemokine SDF-1 stimulates integrin- mediated attest of CD34+ cells on vascular endothelium under shear flow. J Clin. Invest. 104:1199-1211, 1999
Philip S, Bulbule A, Kundu GC. Osteopontin stimulates tumor growth and activation of promatrix metalloproteinase-2 through nuclear factor-kappa B- mediated induction of membrane type 1 matrix metalloproteinase in murine melanoma cells. J. Biol. Chem. 2001; 276:44926-35.
Phillips R., Ager A.:Activation of pertussis toxin-sensitive CXCL12 (SDF- 1) receptors mediates transendothelial migration of T lymphocytes across lymph node high endothelial cells. Eur. J. Immun.32: 837-847,2002
Qin Yu, and Ivan Stamenkovic. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis. Genes Dev. 2000 Jan 15; 14 (2): 163-76.
Rezaie P., Trillo-Pzaos G., Everall LP., Male D.K.:Expression of β- chemokines and chemokine receptors in human fetal astrocytr and microglial co- culture: potential role of chemokines in the developing CNS. Glia 37:64-76, 2002
Rosenberg GA. Matrix metalloproteinases in neuroinflammation. GLIA. 2002; 39: 279-291.
Rossi, D. and Zlotnik, A. The biology of chemokines and their receptors. Annu Rev Immunol, 18: 217-242, 2000.
Schols D., Struyf S., Van Damme J., Este J. E., Henson G., De Clercq E. Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J. Exp. Med., 186: 1383-1388, 1997.
Sehgal, A., Ricks, S., Boynton, A. L., Warrick, J., and Murphy, G. P. Molecular characterization of CXCR-4: a potential brain tumor-associated gene. J. Surg. Oncol., 69: 239-248, 1998.
Sternlicht MD and Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001; 17: 463-516.
Taichman, R. S., Cooper, C., Keller, E. T., Pienta, K. J., Taichman, N. S., and McCauley, L. K. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res, 62: 1832-1837, 2002.
Ticchioni M., Charvet C., Noraz N., Lamy L., Steinberg M., Bernard A., Deckert M.:Signaling through ZAP-70 is required for CXCL12-mediated T-cell transendothelial migration. Blood, 99, No.9, May 1:3111-3118, 2002
Wang J.F., Park I-W., Groopman J.E.:Stromal cell-derived factor-1αstimulate tyrosine phosphorylation of mutiple focal adhesion protein and induces migration of hematopoietic progenitor cells: roles of phosphoinositide- 3 kinase and protein kinase C. Blood 95, No.8, April 15:2502-2513, 2000
Wang X, Mori T, Jung JC, Fini ME, Lo EH. Secretion of matrix metalloproteinase-2 and -9 after mechanical trauma injury in rat cortica cultures and involvement of MAP kinase. J. Neurotrauma. 2002; 19:615-25.
Webb CP, Taylor GA, Jeffers M, Fiscella M, Oskarsson M, Resau JH, Vande Woude GF. Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis. Oncogene 1998: 17: 2019-2025.
Welch DR, Sakamaki T, Pioquinto R, Leonard TO, Goldberg SF, Hon Q, Erikson RL, Rieber M, Rieber MS, Hicks DJ, Bonventre JV, Alessandrini A. Transfection of constitutively active mitogen-activated protein/extracellular signal- regulated kinase kinase confers tumorigenic and metastatic potentials to NIH3T3 cells. Cancer Res. 2000; 60:1552-6.
Wells T.N.,Power C.A., Lusti-Narasimhan M., Hoogewerf A.J., Cooke R.M., Chung C.W., Peotsh M.C, Proudfoot A.E.:Selectivity and antagonist, of chemokine receptors. J. Leuk. Biol.,59:53-60, 1996
Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999; 13:781-92.
Xia, M., Leppert, D., Hauser, S. L., Sreedharan, S. P., Nelson, P. J., Krensky, A. M., and Goetzl, E. J. Stimulus specificity of matrix metalloproteinase dependence of human T cell migration through a model basement membrane (1996) J. Immunol. 156, 160-167
Yoshida M, Korfhagen TR, Whitsett JA. Surfactant protein D regulates NF- kappa B and matrix metalloproteinase production in alveolar macrophages via oxidant-sensitive pathways. J. Immunol. 2001; 166:7514-9.
Zhang X-F., Wang J-F., Matczak E., Proper J., Groopman J.E:Janus kinase 2 is involved in stromal cell- derived factor-1α- induced tyrosine phosphorylation of focal adhesion proteins and migration. Blood, 100, No.8 October 15:3342-3348, 2001
Zhang Y, Thant AA, Machida K, Ichigotani Y, Naito Y, Hiraiwa Y, Senga T, Sohara Y, Matsuda S, Hamaguchi M. Hyaluronan-CD44s signaling regulates matrix metalloproteinase-2 secretion in a human lung carcinoma cell line QG90. CancerRes. 2002; 62: 3962-3965.
Zhou, Y., Larsen, P. H., Hao, C., and Yong, V. W. CXCR4 is a major chemokine receptor on glioma cells and mediates their survival. J Biol Chem, 277: 49481-49487, 2002.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文