结肠癌血管生成拟态的形态学观察及生成机制
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摘要
目的:探讨结肠癌血管生成拟态(VM)现象及其生成的相关机制。
方法:体外三维培养结肠癌细胞株SW480,倒置显微镜下观察VM形成情况,透射电镜下观察其超微结构。采用MTT法检测磷脂酰肌醇-3激酶(PI-3K)信号通路抑制剂2-(4-吗啉基)-8-苯基-4氢-1-苯并吡喃-4-酮(LY294002 )对SW480细胞的增殖抑制率。10μmo1/L LY294002处理SW480细胞72 h,在光学显微镜下观察VM密度,并用逆转录聚合酶链技术(RT-PCR)检测骨桥蛋白(OPN)基因,基质金属蛋白酶2(MMP2)基因的水平。Western Blot法检测10μmo1/L LY294002处理SW480细胞24～72 h后蛋白激酶B (PKB),磷酸化蛋白激酶B (p-PKB)蛋白的表达。
结果:结肠癌细胞株SW480在体外三维培养条件下能够形成VM,电镜观察结果进一步证实了VM的存在。LY294002作用后SW480细胞的生长明显减慢,抑制率为13.01%～67.55%( P<0.01)且呈良好的时间-剂量效应关系。SW480细胞经10μmo1/L LY294002干预72 h后,VM密度由12.50±3.27下降至2.60±1.07( P<0.01),opn,mmp2 mRNA的表达强度分别为0.31±0.01,0.20±0.04,低于未干预细胞的表达强度0.75±0.03,0.55±0.05 (P<0.01)。10μmo1/L LY294002处理SW480细胞24～72 h后,PKB蛋白表达下降( P<0.01), p-PKB蛋白表达水平无明显变化。
结论:LY294002通过下调opn,mmp2 mRNA的表达,抑制结肠癌细胞VM的形成,此过程与抑制PI-3K/PKB通路有关。
AIM: To explore whether vasculogenic mimicry (VM) exists in colon carcinoma and the possible mechanism.
METHODS: Three-dimensional culture system of human colon carcinoma cell line SW480 was constructed to observe VM under inverted microscope, and the ultrastructure of VM was observed under trans-electron microscope. The proliferation inhibitory rates of SW480 cells induced by the specific inhibitor 2-(4-morpholinyl)-8-phenyl -4H-1-benzopyran-4-one (LY294002) of the signaling pathway phosphatidy1inosito1-3 kinase (PI-3K) were detected by Methyl thiazolyl tetrazolium (MTT) method. After SW480 cells were treated with 10μmo1/L LY294002 for 72 h, the density of VM was observed under light microscope. Moreover, the expressions of osteopontin (OPN), matrix metalloproteinase2 (MMP2) genes were assessed by reverse transcription-polymerase chain reaction (RT-PCR). After SW480 cells were treated with 10μmo1/L LY294002 for 24-72 h, the expressions of protein kinase B (PKB), phospho-protein kinase B (p-PKB) proteins were analyzed by Western Blot.
RESULTS: During Three-dimensional culture, SW480 cells can form VM. The result of trans-electron microscope validated the presence of VM. After LY294002 treatment,the growth of SW480 cells was inhibited significantly in a time and dose dependent manner, and the inhibition rates were 13.01%-67.55% ( P< 0.01) .When treated for 72 h ,The density of VM was decreased from [( 12.50±3.27 ) to ( 2.60±1.07) ,P< 0.01] , the expressions of opn, mmp2 genes were lower in 10μmo1/L LY294002 groups than in control groups [ (0.31±0.01) vs (0.75±0 .03) , (0.20±0 .04 ) vs (0.55±0 .05 ), P<0.0 1 ]. The expression of p-PKB protein was down-regulated ( P<0.01), but it had no change on PKB.
CONCLUSION: LY294002 can inhibit the formation of VM in colon carcinoma by reducing opn and mmp2 expression, which might be related to the inhibition of PI3K/PKB signaling pathway.
方法:体外三维培养结肠癌细胞株SW480,倒置显微镜下观察VM形成情况,透射电镜下观察其超微结构。采用MTT法检测磷脂酰肌醇-3激酶(PI-3K)信号通路抑制剂2-(4-吗啉基)-8-苯基-4氢-1-苯并吡喃-4-酮(LY294002 )对SW480细胞的增殖抑制率。10μmo1/L LY294002处理SW480细胞72 h,在光学显微镜下观察VM密度,并用逆转录聚合酶链技术(RT-PCR)检测骨桥蛋白(OPN)基因,基质金属蛋白酶2(MMP2)基因的水平。Western Blot法检测10μmo1/L LY294002处理SW480细胞24～72 h后蛋白激酶B (PKB),磷酸化蛋白激酶B (p-PKB)蛋白的表达。
结果:结肠癌细胞株SW480在体外三维培养条件下能够形成VM,电镜观察结果进一步证实了VM的存在。LY294002作用后SW480细胞的生长明显减慢,抑制率为13.01%～67.55%( P<0.01)且呈良好的时间-剂量效应关系。SW480细胞经10μmo1/L LY294002干预72 h后,VM密度由12.50±3.27下降至2.60±1.07( P<0.01),opn,mmp2 mRNA的表达强度分别为0.31±0.01,0.20±0.04,低于未干预细胞的表达强度0.75±0.03,0.55±0.05 (P<0.01)。10μmo1/L LY294002处理SW480细胞24～72 h后,PKB蛋白表达下降( P<0.01), p-PKB蛋白表达水平无明显变化。
结论:LY294002通过下调opn,mmp2 mRNA的表达,抑制结肠癌细胞VM的形成,此过程与抑制PI-3K/PKB通路有关。
AIM: To explore whether vasculogenic mimicry (VM) exists in colon carcinoma and the possible mechanism.
METHODS: Three-dimensional culture system of human colon carcinoma cell line SW480 was constructed to observe VM under inverted microscope, and the ultrastructure of VM was observed under trans-electron microscope. The proliferation inhibitory rates of SW480 cells induced by the specific inhibitor 2-(4-morpholinyl)-8-phenyl -4H-1-benzopyran-4-one (LY294002) of the signaling pathway phosphatidy1inosito1-3 kinase (PI-3K) were detected by Methyl thiazolyl tetrazolium (MTT) method. After SW480 cells were treated with 10μmo1/L LY294002 for 72 h, the density of VM was observed under light microscope. Moreover, the expressions of osteopontin (OPN), matrix metalloproteinase2 (MMP2) genes were assessed by reverse transcription-polymerase chain reaction (RT-PCR). After SW480 cells were treated with 10μmo1/L LY294002 for 24-72 h, the expressions of protein kinase B (PKB), phospho-protein kinase B (p-PKB) proteins were analyzed by Western Blot.
RESULTS: During Three-dimensional culture, SW480 cells can form VM. The result of trans-electron microscope validated the presence of VM. After LY294002 treatment,the growth of SW480 cells was inhibited significantly in a time and dose dependent manner, and the inhibition rates were 13.01%-67.55% ( P< 0.01) .When treated for 72 h ,The density of VM was decreased from [( 12.50±3.27 ) to ( 2.60±1.07) ,P< 0.01] , the expressions of opn, mmp2 genes were lower in 10μmo1/L LY294002 groups than in control groups [ (0.31±0.01) vs (0.75±0 .03) , (0.20±0 .04 ) vs (0.55±0 .05 ), P<0.0 1 ]. The expression of p-PKB protein was down-regulated ( P<0.01), but it had no change on PKB.
CONCLUSION: LY294002 can inhibit the formation of VM in colon carcinoma by reducing opn and mmp2 expression, which might be related to the inhibition of PI3K/PKB signaling pathway.
引文
[1] Maniotis A J, Folberg R, Hess A,et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry [J].Am J Pathol, 1999, 155 (3):739-752.
[2] Folberg R,Maniotis A.Vasculogenic mimicry[J].APMIS 2004,112:508-525.
[3] Anguste P, Lemiere S, Larrieu-Lahargue F, et al. Molecular mechanisms of tumor vascularization[J]. Grit Rev Oncol Hematol, 2005, 54(1): 53-61.
[4] Zhang G, Huang Z, Shi R, et al. Osteopontin regulation by protein kinase B(Akt)in HepG2 cells[J]. Exp Oncol, 2006, 28(1):36-39.
[5] Liu SJ, Hu GF, Liu YJ, et al. Effect of human osteopontin on proliferation, transmigration and expression of MMP-2 and MMP-9 in osteosarcoma cells[J], Chin Med J(Eng1), 2004, 117:235-240.
[6]焦南林,王娟,郑杰.骨桥蛋白下调对乳腺癌细胞生物学行为及MMP-2表达的影响[J].肿瘤, 2007, 27(12):939-943.
[7] Sood AK, Fletcher MS, Coffin JE, et a1. Functional role of matrix metalloproteinases in ovarian tumor cell plasticity[J]. Am J Obstet Gyneco1, 2004, 190:899-909.
[8] Kadkol S S, Lin A Y, Barak V, et a1. Osteopontin expression and serum levels in metastatic uveal melanoma:a pilot study[J]. Investigative Ophthalmology and Visual Science. 2006, 47: 802-806.
[9] Hendrix MJ, Seftor EA, Hess AR, et al. Vasculogenic mimicry and tumour cell plasticity: lessons from melanoma [J]. Nat Rev Cancer, 2003, 3(6): 411-421.
[10] Zhang S, Guo H, Zhang D, et a1.Oncol Rep.2006;15(1):15-20.
[11] Zhang S, Zhang D, Sun B. Vasculogenic mimicry: Current status and future prospects[J]. Cancer Lett, 2007, 254(2):157-164.
[12]夏振龙.大肠癌肝转移的发生率及临床特点[J].中国实用外科杂志,1999.19(10):579.
[13] Chang F,Lee JT,Navolanic PM,et a1.Involvement of PI3K/Akt pathway in cell cycle progression.apoptosis.and neoplastic transformation:a target for cancer chemotherapy[J].Leukemia,2003,17(3):590-603.
[14] Hess AR,Seftor EA,Seftor RE,et al.Phosphoinostide 3-kinase regulates membrane typel-matrix Metalloproteinase(MMP)and MMP-2 activity during Melanoma cell vasculogenic mimicry[J].Cancer Res,2003;63 ( 16 ) :4757-4762.
[15]赵灵芝,银巍,苏兴文,等. IGF-1经PI3K/Akt依赖性途径保护苯妥英诱导的小脑颗粒神经元凋亡[J].中国药理学通报, 2005, 21(1): 53-57.
[16] Sood AK, Seftor EA , Fletcher MS , et al. Molecular determinant s of ovarian cancer plasticity[J].Am J Pat hol ,2001 , 158 (4) : 1279-1288.
[17] Seftor R E , Seftor E A , Koshikawa N, et al. Cooperative interactions of laminin-5 gamma-2 chain, matrix metalloproteinase-2 and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma[J]. Cancer Res, 2001, 61(17): 6322-6327.
[18] Junaid A, Amara F M. Osteopontin: correlation with interstitial fibrosis in human diabetic kidney and PI3-kinase-mediated enhancement of expression by glucose in human proximal tubular epithelial cells[J]. Histopathology, 2004, 44(2): 136-146.
[19] Zhang G, He B, Weber G F, et a1. Growth factor signaling induces metastasis genes in transforlned cells: molecular connection between Akt kinase and osteopontin in breast cancer[J]. Mol Cell Biol, 2003, 23(18): 6507-6519.
[1]. Maniotis AJ,Folberg R,Hess A,et al.Vascular Channel formation by human melanoma cells in Vivo and vitro:vasculogenic mimicry[J].AM J Pathol,1999,155(3):739-752.
[2]. Folberg R,Hendrix MJ,Maniotis AJ.Vasculogenic mimicry and Tumor angiogenesis[J].Am J Pathol,2000,156(2):361-381.
[3]. Folberg R, Maniotis AJ. Vasculogenic mimicry[J]. APMIS, 2004, 112(7-8):508-525.
[4]. Zhang S, Zhang D, Sun B. Vasculogenic mimicry: Current status and future prospects[J]. Cancer Lett, 2007, 254(2):157-164.
[5]. Hendrix MJ, Seftor EA, Hess AR, et al. Vasculogenic mimicry and tumour - cell plasticity: lessons from melanoma [J]. Nat Rev Cancer, 2003, 3(6): 411-421.
[6]. Zhang S,Guo H,Zhang D.et a1.Oncol Rep.2006;15(1):15-20.
[7]Hendrix M J, Seftor R E. Seftor E A.et a1.Transendothelial function of human metastatic melanoma cells : role of the microenvironment in cell-fate determination[J].Cancer Res,2002,62(3):665-668.
[8]Cvrioglu AS,Yilmaz S,Koken T,et a1.Comparison of the effects of low intra-abdominal pressure and ischemic preconditioning on the generation of oxidative stress markers and inflammatory cytokines during laparoscopy in rats. Hum Reprod ,2004,19(9):2144-2151.
[9]张诗武,孙保存等。不同微环境对黑色素瘤细胞侵袭能力和局部微环境循环模式形成的影响。中华病理学杂志,2007,36(12):8327
[10].Kim sJ,Rabbani ZN,Dewhirst MW .et a1. Expression of HIF-1alpha,CA IX ,VEGF,and MMP-9 in surgically resected non-small cell lung cancer.LungCancer,2005,49(3):325-335.
[11].Yao LQ,Feng JX,Ding JX,et al.Primary study of vasculogenic mimicry induced by hypoxion in epithelial ovaria carcinoma[J].Zhonghua Fu Chan Ke Za Zhi,2005;40(10):662-665
[12]. Bittner M ,Meltzer P,Chen Y,et a1.Molecular classification of cutaneous malignant melanoma by gene expression profiling[J].Nature,2000,406(6795):536-540.
[13]. Ramalho-Santos M ,Yoon S,Matsuzaki Y,et a1“.Stemness”:transcriptional profiling of embryonic and adult stem cells[J].Science 2002,298(5593):597-600.
[14]. Folberg R , Arbieva Z , Moses J , et al . Tumor cell plasticity in uveal melanoma : microenvironment directed dampening of the invasive and metastatic genotype and phenotype accompanies the generation of vasculogenic mimicry patterns [ J ] . Am J Pat hol , 2006 , 169 (4) , 1376-1389.
[15]. Ruf W ,Softor EA,Petrovan RJ,et a1.Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry[J].Cancer Res,2003,63(17):5381-5389.
[16].Hess AR,Seftor EA,Gardner LM,et a1.Molecular regulation of tumor cell vasculogenic mimicry by tyrosine phosphorylation:role of epithelial cell kinase(Eck/EphA2)[J],Cancer Res,2001,61(8):3250-3255.
[17].Hendrix MJ,Seflor EA,Hess AR,et a1.Molecular plasticity of human melanoma cells[J].Oncogene,2003,22(20):3070-3075.
[18].Brantley-Sieders DM,Caughron J,Hicks D,et a1.EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Racl GTPase activation[J].J Cell Sci,2004,117(10):2037-2049.
[19].Hess AR.Hendrix MJ Cell Cycle,2006;5(5):478_480
[20].Hess AR,Seftor EA,Gruman LM ,et a1 Cancer Biol Ther,2006:5(2):228_233
[21] Hess AR , Seftor EA , Seftor RE , et a1. Phosphoinositide 3-Kinase regulatesmembrane type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry [J ] . Cancer Res , 2003 , 63 (16) : 4757 - 4762.
[22].Seftor RE,Seftor EA,Koshikawa N,et a1.Cooperative interactions of laminin 5γ2 chain,matrix metalloproteinase-2,and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma[J].Cancer Res,2001,61(17):6322-6327.
[23] .Kerbel RS , Kamen BA . The anti-angiogenie basis of metronomic chemotherapy[J].Nat Rev Cancer,2004,4(6):423-436.
[24].Kobayashi H, Shirakawa K, Kawamoto S, Saga T,Sato N, Hiraga A, Watanabe I, Heike Y, Togashi K, Konishi J, Brechbiel MW, Wakasugi H. Rapid accumulation and internalization of radiolabeled herceptin in an inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M-Gd)(256).Cancer Res 2002; 62: 860-866.
[25]. Petty AP, Garman KL,Winn VD, et al. Overexpression of carcinoma and embryonic cytotrophoblast cell specific Mig-7 induces invasion and vessel-like structure formation[ J ]. Am J Pathol, 2007,170 (5) : 1763 - 1780.
[26]Kadkol SS, Lin AY, Barak V, et a1. Osteopontin expression and serum levels in metastatic uveal melanoma:A pilot study[J]. Investigative Ophthalmology and Visual Science,2006, 47:802-806.
[2] Folberg R,Maniotis A.Vasculogenic mimicry[J].APMIS 2004,112:508-525.
[3] Anguste P, Lemiere S, Larrieu-Lahargue F, et al. Molecular mechanisms of tumor vascularization[J]. Grit Rev Oncol Hematol, 2005, 54(1): 53-61.
[4] Zhang G, Huang Z, Shi R, et al. Osteopontin regulation by protein kinase B(Akt)in HepG2 cells[J]. Exp Oncol, 2006, 28(1):36-39.
[5] Liu SJ, Hu GF, Liu YJ, et al. Effect of human osteopontin on proliferation, transmigration and expression of MMP-2 and MMP-9 in osteosarcoma cells[J], Chin Med J(Eng1), 2004, 117:235-240.
[6]焦南林,王娟,郑杰.骨桥蛋白下调对乳腺癌细胞生物学行为及MMP-2表达的影响[J].肿瘤, 2007, 27(12):939-943.
[7] Sood AK, Fletcher MS, Coffin JE, et a1. Functional role of matrix metalloproteinases in ovarian tumor cell plasticity[J]. Am J Obstet Gyneco1, 2004, 190:899-909.
[8] Kadkol S S, Lin A Y, Barak V, et a1. Osteopontin expression and serum levels in metastatic uveal melanoma:a pilot study[J]. Investigative Ophthalmology and Visual Science. 2006, 47: 802-806.
[9] Hendrix MJ, Seftor EA, Hess AR, et al. Vasculogenic mimicry and tumour cell plasticity: lessons from melanoma [J]. Nat Rev Cancer, 2003, 3(6): 411-421.
[10] Zhang S, Guo H, Zhang D, et a1.Oncol Rep.2006;15(1):15-20.
[11] Zhang S, Zhang D, Sun B. Vasculogenic mimicry: Current status and future prospects[J]. Cancer Lett, 2007, 254(2):157-164.
[12]夏振龙.大肠癌肝转移的发生率及临床特点[J].中国实用外科杂志,1999.19(10):579.
[13] Chang F,Lee JT,Navolanic PM,et a1.Involvement of PI3K/Akt pathway in cell cycle progression.apoptosis.and neoplastic transformation:a target for cancer chemotherapy[J].Leukemia,2003,17(3):590-603.
[14] Hess AR,Seftor EA,Seftor RE,et al.Phosphoinostide 3-kinase regulates membrane typel-matrix Metalloproteinase(MMP)and MMP-2 activity during Melanoma cell vasculogenic mimicry[J].Cancer Res,2003;63 ( 16 ) :4757-4762.
[15]赵灵芝,银巍,苏兴文,等. IGF-1经PI3K/Akt依赖性途径保护苯妥英诱导的小脑颗粒神经元凋亡[J].中国药理学通报, 2005, 21(1): 53-57.
[16] Sood AK, Seftor EA , Fletcher MS , et al. Molecular determinant s of ovarian cancer plasticity[J].Am J Pat hol ,2001 , 158 (4) : 1279-1288.
[17] Seftor R E , Seftor E A , Koshikawa N, et al. Cooperative interactions of laminin-5 gamma-2 chain, matrix metalloproteinase-2 and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma[J]. Cancer Res, 2001, 61(17): 6322-6327.
[18] Junaid A, Amara F M. Osteopontin: correlation with interstitial fibrosis in human diabetic kidney and PI3-kinase-mediated enhancement of expression by glucose in human proximal tubular epithelial cells[J]. Histopathology, 2004, 44(2): 136-146.
[19] Zhang G, He B, Weber G F, et a1. Growth factor signaling induces metastasis genes in transforlned cells: molecular connection between Akt kinase and osteopontin in breast cancer[J]. Mol Cell Biol, 2003, 23(18): 6507-6519.
[1]. Maniotis AJ,Folberg R,Hess A,et al.Vascular Channel formation by human melanoma cells in Vivo and vitro:vasculogenic mimicry[J].AM J Pathol,1999,155(3):739-752.
[2]. Folberg R,Hendrix MJ,Maniotis AJ.Vasculogenic mimicry and Tumor angiogenesis[J].Am J Pathol,2000,156(2):361-381.
[3]. Folberg R, Maniotis AJ. Vasculogenic mimicry[J]. APMIS, 2004, 112(7-8):508-525.
[4]. Zhang S, Zhang D, Sun B. Vasculogenic mimicry: Current status and future prospects[J]. Cancer Lett, 2007, 254(2):157-164.
[5]. Hendrix MJ, Seftor EA, Hess AR, et al. Vasculogenic mimicry and tumour - cell plasticity: lessons from melanoma [J]. Nat Rev Cancer, 2003, 3(6): 411-421.
[6]. Zhang S,Guo H,Zhang D.et a1.Oncol Rep.2006;15(1):15-20.
[7]Hendrix M J, Seftor R E. Seftor E A.et a1.Transendothelial function of human metastatic melanoma cells : role of the microenvironment in cell-fate determination[J].Cancer Res,2002,62(3):665-668.
[8]Cvrioglu AS,Yilmaz S,Koken T,et a1.Comparison of the effects of low intra-abdominal pressure and ischemic preconditioning on the generation of oxidative stress markers and inflammatory cytokines during laparoscopy in rats. Hum Reprod ,2004,19(9):2144-2151.
[9]张诗武,孙保存等。不同微环境对黑色素瘤细胞侵袭能力和局部微环境循环模式形成的影响。中华病理学杂志,2007,36(12):8327
[10].Kim sJ,Rabbani ZN,Dewhirst MW .et a1. Expression of HIF-1alpha,CA IX ,VEGF,and MMP-9 in surgically resected non-small cell lung cancer.LungCancer,2005,49(3):325-335.
[11].Yao LQ,Feng JX,Ding JX,et al.Primary study of vasculogenic mimicry induced by hypoxion in epithelial ovaria carcinoma[J].Zhonghua Fu Chan Ke Za Zhi,2005;40(10):662-665
[12]. Bittner M ,Meltzer P,Chen Y,et a1.Molecular classification of cutaneous malignant melanoma by gene expression profiling[J].Nature,2000,406(6795):536-540.
[13]. Ramalho-Santos M ,Yoon S,Matsuzaki Y,et a1“.Stemness”:transcriptional profiling of embryonic and adult stem cells[J].Science 2002,298(5593):597-600.
[14]. Folberg R , Arbieva Z , Moses J , et al . Tumor cell plasticity in uveal melanoma : microenvironment directed dampening of the invasive and metastatic genotype and phenotype accompanies the generation of vasculogenic mimicry patterns [ J ] . Am J Pat hol , 2006 , 169 (4) , 1376-1389.
[15]. Ruf W ,Softor EA,Petrovan RJ,et a1.Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry[J].Cancer Res,2003,63(17):5381-5389.
[16].Hess AR,Seftor EA,Gardner LM,et a1.Molecular regulation of tumor cell vasculogenic mimicry by tyrosine phosphorylation:role of epithelial cell kinase(Eck/EphA2)[J],Cancer Res,2001,61(8):3250-3255.
[17].Hendrix MJ,Seflor EA,Hess AR,et a1.Molecular plasticity of human melanoma cells[J].Oncogene,2003,22(20):3070-3075.
[18].Brantley-Sieders DM,Caughron J,Hicks D,et a1.EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Racl GTPase activation[J].J Cell Sci,2004,117(10):2037-2049.
[19].Hess AR.Hendrix MJ Cell Cycle,2006;5(5):478_480
[20].Hess AR,Seftor EA,Gruman LM ,et a1 Cancer Biol Ther,2006:5(2):228_233
[21] Hess AR , Seftor EA , Seftor RE , et a1. Phosphoinositide 3-Kinase regulatesmembrane type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry [J ] . Cancer Res , 2003 , 63 (16) : 4757 - 4762.
[22].Seftor RE,Seftor EA,Koshikawa N,et a1.Cooperative interactions of laminin 5γ2 chain,matrix metalloproteinase-2,and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma[J].Cancer Res,2001,61(17):6322-6327.
[23] .Kerbel RS , Kamen BA . The anti-angiogenie basis of metronomic chemotherapy[J].Nat Rev Cancer,2004,4(6):423-436.
[24].Kobayashi H, Shirakawa K, Kawamoto S, Saga T,Sato N, Hiraga A, Watanabe I, Heike Y, Togashi K, Konishi J, Brechbiel MW, Wakasugi H. Rapid accumulation and internalization of radiolabeled herceptin in an inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M-Gd)(256).Cancer Res 2002; 62: 860-866.
[25]. Petty AP, Garman KL,Winn VD, et al. Overexpression of carcinoma and embryonic cytotrophoblast cell specific Mig-7 induces invasion and vessel-like structure formation[ J ]. Am J Pathol, 2007,170 (5) : 1763 - 1780.
[26]Kadkol SS, Lin AY, Barak V, et a1. Osteopontin expression and serum levels in metastatic uveal melanoma:A pilot study[J]. Investigative Ophthalmology and Visual Science,2006, 47:802-806.