山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (3): 81-86.doi: 10.6040/j.issn.1671-7554.0.2019.1257
杨秀婷1,刘启功2,左萍2,刘正湘2,左后娟2
YANG Xiuting1, LIU Qigong2, ZUO Ping2, LIU Zhengxiang2, ZUO Houjuan2
摘要: 目的 研究CD151整合素结合缺陷突变体(CD151-MUT)突变对肺腺癌细胞A549迁移的影响及机制。 方法 分别运用CD151、CD151-MUT和GFP质粒转染肺腺癌A549细胞,作为CD151组、CD151-MUT组和GFP组,同时设置Control组及Reagent组。改良的Boyden趋化小室法检测各组细胞的体外迁移能力。Western blotting方法检测各组细胞CD151蛋白、黏着斑激酶(FAK)及P130Cas蛋白的表达。 结果 (1) CD151组(2.23±0.22)和CD151-MUT组(2.15±0.17)CD151蛋白的表达较Control组(1.03±0.15)、GFP组(1.18±0.13)和Reagent组(1.22±0.11)均增高,5组均值差异有统计学意义(F=39.8,P<0.001),但两两多重比较显示CD151组和CD151-MUT组间差异无统计学意义(q=1.007, P=0.628)。(2)CD151组较Control组、GFP组及Reagent组促进肿瘤细胞的迁移(F=15.3, P=0.007),而CD151-MUT组细胞的迁移能力较CD151组下降,差异有统计学意义(q=6.760,P=0.010)。(3)CD151高表达促进p-FAK、p-P130Cas蛋白表达增加(F=16.3,P<0.001; F=10.9,P=0.001),而CD151-MUT组p-FAK 、p-P130Cas蛋白表达水平较CD151组减弱(q=8.620,P=0.010; q=6.859,P=0.009)。 结论 CD151-MUT突变破坏CD151-整合素复合体形成,抑制肿瘤转移。CD151-α3/α6整合素复合体在肿瘤细胞迁移过程中发挥重要作用。
中图分类号:
[1] | Brzozowski JS, Bond DR, Jankowski H, et al. Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion[J]. Sci Rep, 2018, 8(1): 8822. |
[2] | 俞雷来,曹利平. CD151与肿瘤侵袭转移的关系研究进展[J]. 浙江医学, 2017, 39(8): 663-665. |
[3] | Shi GM, Ke AW, Zhou J, et al. CD151 modulates expression of matrix metalloproteinase 9 and promotes neoangiogenesis and progression of hepatocellular carcinoma[J]. Hepatology, 2010, 52(1): 183-196. |
[4] | Yang YM, Zhang ZW, Liu QM, et al. Overexpression of CD151 predicts prognosis in patients with resected gastric cancer[J]. PLoS One, 2013, 8(3): e58990. doi: 10.1371/journal.pone.0058990. |
[5] | Sadej R, Grudowska A, Turczyk L, et al. CD151 in cancer progression and metastasis: a complex scenario[J]. Lab Invest, 2014, 94(1): 41-51. |
[6] | Yu Y, Liang C, Wang S, et al. CD151 promotes cell metastasis via activating TGF-beta1/Smad signaling in renal cell carcinoma[J]. Oncotarget, 2018, 9(17): 13313-13323. |
[7] | Detchokul S, Williams ED, Parker MW, et al. Tetraspanins as regulators of the tumour microenvironment: implications for metastasis and therapeutic strategies[J]. Br J Pharmacol, 2014, 171(24): 5462-5490. |
[8] | Berditchevski F. Complexes of tetraspanins with integrins: more than meets the eye[J]. J Cell Sci, 2001, 114(Pt 23): 4143-4151. |
[9] | Te ML, Juksar J, Harkes R, et al. Tetraspanin CD151 and integrin alpha3beta1 contribute to the stabilization of integrin alpha6beta4-containing cell-matrix adhesions[J]. J Cell Sci, 2019, 132(19). doi: 10.1242/jcs.235366. |
[10] | Kazarov AR, Yang X, Stipp CS, et al. An extracellular site on tetraspanin CD151 determines alpha 3 and alpha 6 integrin-dependent cellular morphology[J]. J Cell Biol, 2002, 158(7): 1299-1309. |
[11] | Liu WF, Zuo HJ, Chai BL, et al. Role of tetraspanin CD151-alpha3/alpha6 integrin complex: implication in angiogenesis CD151-integrin complex in angiogenesis[J]. Int J Biochem Cell Biol, 2011, 43(4): 642-650. |
[12] | 刘伟峰,于晓晖,左后娟,等. rAAV-CD151-AAA194-196表达对大鼠缺血后肢血管新生的影响[J]. 华中科技大学学报(医学版), 2011, 40(5): 525-528. LIU Weifeng, YU Xiaohui, ZUO Houjuan, et al. Effect of rAAV-CD151-AAA194-196 expression on angiogenesis of rat ischemia hind-limb [J]. Acta Med Univ Sci Technol Huazhong, 2011, 40(5): 525-528. |
[13] | Zeng P, Wang YH, Si M, et al. Tetraspanin CD151 as an emerging potential poor prognostic factor across solid tumors: a systematic review and meta-analysis[J]. Oncotarget, 2017, 8(3): 5592-5602. |
[14] | Kwon MJ, Park S, Choi JY, et al. Clinical significance of CD151 overexpression in subtypes of invasive breast cancer[J]. Br J Cancer, 2012, 106(5): 923-930. |
[15] | 李科,洪志鹏,沈丽达,等. CD151及整合素α3β1蛋白在非小细胞肺癌中的表达及意义[J]. 中国全科医学, 2014, 17(5): 531-535. LI Ke, HONG Zhipeng, SHEN Lida, et al. CD151 and integrinα3β1 expression in non-small cell lung cancer[J]. Chinese General Practice, 2014, 17(5): 531-535. |
[16] | Kumari S, Devi GT, Badana A, et al. CD151-a striking marker for cancer therapy[J]. Biomark Cancer, 2015, 7: 7-11. doi: 10.4137/BIC.S21847. |
[17] | Zevian S, Winterwood NE, Stipp CS. Structure-function analysis of tetraspanin CD151 reveals distinct requirements for tumor cell behaviors mediated by alpha3beta1 versus alpha6beta4 integrin[J]. J Biol Chem, 2011, 286(9): 7496-7506. |
[18] | Sterk LM, Geuijen CA, van den Berg JG, et al. Association of the tetraspanin CD151 with the laminin-binding integrins alpha3beta1, alpha6beta1, alpha6beta4 and alpha7beta1 in cells in culture and in vivo[J]. J Cell Sci, 2002, 115(Pt 6): 1161-1173. |
[19] | Yauch RL, Kazarov AR, Desai B, et al. Direct extracellular contact between integrin alpha(3)beta(1)and TM4SF protein CD151[J]. J Biol Chem, 2000, 275(13): 9230-9238. |
[20] | Nishiuchi R, Sanzen N, Nada S, et al. Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151[J]. Proc Natl Acad Sci U S A, 2005, 102(6): 1939-1944. |
[21] | Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applications[J]. Nat Rev Cancer, 2014, 14(9): 598-610. |
[22] | Yang X, Li S, Zhong J, et al. CD151 mediates netrin-1-induced angiogenesis through the Src-FAK-Paxillin pathway[J]. J Cell Mol Med, 2017, 21(1): 72-80. |
[23] | Almeida EA, Ilic D, Han Q, et al. Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase[J]. J Cell Biol, 2000, 149(3): 741-754. |
[24] | Wang Y, Mcniven MA. Invasive matrix degradation at focal adhesions occurs via protease recruitment by a FAK-p130Cas complex[J]. J Cell Biol, 2012, 196(3): 375-385. |
[25] | Liu X, Yan Z, Huang L, et al. Cell surface heat shock protein 90 modulates prostate cancer cell adhesion and invasion through the integrin-beta1/focal adhesion kinase/c-Src signaling pathway[J]. Oncol Rep, 2011, 25(5): 1343-1351. |
[1] | 王雪,李倩,王莉,孙书珍,马爱华. CXCL16基因沉默减轻ox-LDL对小鼠足细胞损伤[J]. 山东大学学报(医学版), 2016, 54(6): 16-21. |
[2] | 袁冰,李冉冉,韩明勇. 恶性黑色素瘤调节肺组织微环境并促进肿瘤肺转移的实验研究[J]. 山东大学学报(医学版), 2016, 54(11): 13-18. |
[3] | 高鹏, 沈方臻, 肖文静, 修元德, 周玲玲. IB期非小细胞肺癌Runx2、Ezrin表达与术后转移的相关性[J]. 山东大学学报(医学版), 2015, 53(1): 63-66. |
[4] | 朱玉广,朱艳,王杰,钟莹莹,杜孝楠,张荣. 整合素-β1在转化生长因子-β2诱导晶状体上皮细胞转化中的作用[J]. 山东大学学报(医学版), 2012, 50(11): 58-. |
[5] | 殷宪明1,董白桦1,张韵2,苏士利1,董召刚2,曲迅2. 正常早孕及稽留流产患者NK细胞中整合素αvβ3的表达分析[J]. 山东大学学报(医学版), 2011, 49(6): 140-. |
[6] | 姜英俊1,2,孔心涓3,张可爽3,胡三元1. c-Met在大肠癌中的表达及在大肠癌发生发展中的作用[J]. 山东大学学报(医学版), 2011, 49(5): 90-93. |
[7] | 王勇,张娇,任万华,李涛. MTA1、nm23、c-myc在肝癌组织中的表达及其相关性[J]. 山东大学学报(医学版), 2011, 49(1): 99-. |
[8] | 陈强1,2,吕家驹1,荆涛2,李玉军3. 基质金属蛋白酶-2和趋化因子受体4在肾透明细胞癌组织中的表达及其临床意义[J]. 山东大学学报(医学版), 2010, 48(6): 107-. |
[9] | 黄先亮1,董白桦1,胡微煦2,王庆杰2,宋丙凤2,王春娥2,刘佳2,孔北华1,曲迅2. 妊娠早期CD56brightCD16- NK细胞CD49d和CD11b的表达分析[J]. 山东大学学报(医学版), 2010, 48(5): 97-100. |
[10] | 刘文婷,孙青. DC-LAMP与DC-SIGN在寻常型银屑病皮损中的表达[J]. 山东大学学报(医学版), 2010, 48(4): 136-138. |
[11] | 李军1,2,王洲1,李树海3,李玉4. ABH及Lewis组织-血型抗原异常表达与原发肺癌生物学行为的相关性研究[J]. 山东大学学报(医学版), 2010, 48(4): 124-129. |
[12] | 孟龙,张阳德,王一兵. 非小细胞肺癌中VEGF-C、CD44v6的表达及临床意义[J]. 山东大学学报(医学版), 2010, 48(4): 83-86. |
[13] | 龙成凤,林殿杰,崔纪云,万云焱 . Galectin3与肺腺癌淋巴及胸膜转移的关系[J]. 山东大学学报(医学版), 2009, 47(01): 72-75. |
[14] | 崔亚洲,贾 青,王兆朋,王朝霞,田 美,张月英,张维东,韩金祥 . 裸鼠胰腺癌高肝转移模型的建立[J]. 山东大学学报(医学版), 2008, 46(8): 739-741. |
[15] | 李增军,孙燕来,李健宁,韩建军 . 结直肠癌根治术后复发转移相关因素分析[J]. 山东大学学报(医学版), 2007, 45(8): 849-851. |
|