窖蛋白1在肿瘤及其血管生成中的作用
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摘要
窖蛋白1(caveolin-1)是胞膜窖(caveolae)上的标志性蛋白,能够识别多种信号分子,与肿瘤的侵袭转移及血管生成等过程密切相关。而caveolin-1在肿瘤血管生成中的作用尚未定论,目前认为caveolin-1在肿瘤及其血管生成中具有促进及抑制双重作用。随着研究的不断深入,caveolin-1很可能成为肿瘤的治疗靶点或早期诊断指标。本文就caveolin-1在肿瘤及其血管生成的作用进行综述。
Caveolin- 1,the marker protein of caveolae,could recognize a variety of signal molecules and might be related to tumor metastasis and angiogenesis. The role of caveolin- 1 in tumor angiogenesis has not been ascertained yet. It has been shown that caveolin- 1 might play a dual function in tumor angiogenesis: either promoting or inhibiting. Caveolin- 1might act as an early diagnostic marker and therapeutic target in carcinoma. This article will review the effects of caveolin-1 on tumor invasion and angiogenesis and discuss the underlying mechanisms.
Caveolin- 1,the marker protein of caveolae,could recognize a variety of signal molecules and might be related to tumor metastasis and angiogenesis. The role of caveolin- 1 in tumor angiogenesis has not been ascertained yet. It has been shown that caveolin- 1 might play a dual function in tumor angiogenesis: either promoting or inhibiting. Caveolin- 1might act as an early diagnostic marker and therapeutic target in carcinoma. This article will review the effects of caveolin-1 on tumor invasion and angiogenesis and discuss the underlying mechanisms.
引文
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[2]Couet J,Belanger MM,Roussel E,et al.Cell biology of caveolae and caveolin[J].Adv Drug Deliv Rev,2001,49(3):223-235.
[3]Couet J,Li S,Okamoto T,et al.Identification of peptide and protein ligands for the Caveolin-scaffolding domain.Implications for the interaction of Caveolin with Caveolaeassociated proteins[J].J Biol Chem,1997,272(10):6525-6533.
[4]Mercier I,Jasmin JF,Pavlides S,et al.Clinical and translational implications of the caveolin gene family:lessons from mouse models and human genetic disorders[J].Lab Invest,2009,89(6):614-623.
[5]Senetta R,Stella G,Pozzi E,et al.Caveolin-1 as a promoter of tumour spreading:when,how,where and why[J].J Cell Mol Med,2013,17(3):325-336.
[6]Qin H1,Bollag WB.The caveolin-1 scaffolding domain peptide decreases phosphatidylglycerol levels and inhibits calcium-induced differentiation in mouse keratinocytes[J].PLo S One,2013,8(11):e80946.
[7]Han H,Rosenhouse-Dantsker A,Gnanasambandam R,et al.Silencing of Kir2 channels by caveolin-1:crosstalk with cholesterol[J].J Physiol,2014,592(Pt 18):4025-4038.
[8]Swrd K,Albinsson S,Rippe C.Arterial dysfunction but maintained systemic blood pressure in cavin-1-deficient mice[J].PLo S One,2014,9(3):e92428.
[9]Pavlides S,Gutierrez-Pajares JL,Katiyar S,et al.Caveolin-1 regulates the anti-atherogenic properties of macrophages[J].Cell Tissue Res,2014,358(3):821-831.
[10]Sato M,Hutchinson DS,Halls ML,et al.Interaction with caveolin-1 modulates G protein coupling of mouseβ3-adrenoceptor[J].J Biol Chem,2012,287(24):20674-20688.
[11]郭贵明,吕智.Caveolin-1在肿瘤中的研究进展[J].实用骨科杂志,2009,15(1):33-35,73.
[12]Shen XJ,Zhang H,Tang GS,et al.Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer[J].Int J Biol Sci,2015,11(4):370-379.
[13]Ma W,Wang DD,Li L,et al.Caveolin-1 plays a key role in the oleanolic acid-induced apoptosis of HL-60cells[J].Oncol Rep,2014,32(1):293-301.
[14]Friedrich T,Richter B,Gaiser T,et al.Deficiency of caveolin-1 in Apc(min/+)mice promotes colorectal tumorigenesis[J].Carcinogenesis,2013,34(9):2109-2118.
[15]Xu J,Agyemang S,Qin Y,et al.A Novel Pathway that Links Caveolin-1 Down-Regulation to BRCA1 Dysfunction in Serous Epithelial Ovarian Cancer Cells[J].Enliven Chall Cancer Detect Ther,2014,1(1).pii:004.
[16]Simpkins SA,Hanby AM,Holliday DL,et al.Clinical and functional significance of loss of caveolin-1 expression in breast cancer-associated fibroblasts[J].JPathol,2012,227(4):490-498.
[17]张志波,何庆良,石铮,等.Caveolin-1在肝细胞癌表达及与肿瘤血管生成的关系[J].中国普通外科杂志,2012,21(1):53-57.
[18]Huang C,Qiu Z,Wang L,et al.A novel Fox M1-caveolin signaling pathway promotes pancreatic cancer invasion and metastasis[J].Cancer Res,2012,72(3):655-665.
[19]Li L,Ren C,Yang G,et al.Caveolin-1 promotes autoregulatory,Akt-mediated induction of cancer-promoting growth factors in prostatecancer cells[J].Mol Cancer Res,2009,7(11):1781-1791.
[20]Pancotti F,Roncuzzi L,Maggiolini M,et al.Caveolin-1silencing arrests the proliferation of metastatic lung cancer cells through the inhibition of STAT3 signaling[J].Cell Signal,2012,24(7):1390-1397.
[21]Masuelli L,Budillon A,Marzocchella L,et al.Caveolin-1overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-βcatenins complex and multiple Erb B receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas[J].J Cell Physiol,2012,227(9):3344-3353.
[22]Steffens S,Schrader AJ,Blasig H,et al.Caveolin 1 protein expression in renal cell carcinoma predicts survival[J].BMC Urol,2011,7(11):25.
[23]Bonuccelli G,Casimiro M C,Sotgia F,et al.Caveolin-1(P132L),a common breast cancer mutation,confers mammary cell invasiveness and defines a novel stem cell/metastasis-associated gene signature[J].Am J Pathol,2009,174(5):1650-1662.
[24]袁碧英,易斌,鲁开智,等.Caveolin-1在肿瘤中的作用机制的研究进展[J].中国医学创新,2014,11(6):129-131.
[25]Gratton JP,Lin MI,Yu J,et al.Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice[J].Cancer Cell,2003,4(1):31-39.
[26]Bocci G,Fioravanti A,Orlandi P,et al.Metronomic ceramide analogs inhibit angiogenesis in pancreatic cancer through up-regulation of caveolin-1 and thrombospondin-1 and down-regulation of cyclin D1[J].Neoplasia,2012,14(9):833-845.
[27]Fang K,Fu W,Beardsley AR,et al.Overexpression of caveolin-1 Inhibits endothelial cell proliferation by arresting the Cell Cycle at G[J].Cell Cycle,2007,6(2):199-204.
[28]Ayala G,Morello M,Frolov A,et al.Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression[J].J Pathol,2013,231(1):77-87.
[29]Philip M.Bauer,Jun Yu,Yan Chen,et al.Endothelialspecific expression of caveolin-1 impairs microvascular permeability and angiogenesis[J].PNAS,2005,102(1):204-209.
[30]Zulli A,Buxton BF,Black MJ,et al.The immunoquantification of caveolin-1 and e NOS in human and rabbit diseased blood vessels[J].J Histochem Cytochem,2006,54(2):151-159.
[31]Brouet A,Dewever J,Martinive P,et al.Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide[J].FASEBJ,2005,19(6):602-604.
[32]Zhang ZB,Cai L,Zheng SG,et al.Overexpression of caveolin-1 in hepatocellular carcinoma with metastasis and worse prognosis:correlation with vascular endothelial growth factor,microvessel density and unpaired artery[J].Pathol Oncol Res,2009,15(3):495-502.
[33]Nassar ZD,Moon H,Duong T,et al.PTRF/Cavin-1decreases prostate cancer angiogenesis and lymphangiogenesis[J].Oncotarget,2013,4(10):1844-1855.
[34]Sáinz-Jaspeado M,Huertas-Martinez J,Lagares-Tena L,et al.Eph A2-induced angiogenesis in ewing sarcoma cells works through b FGF production and is dependent on caveolin-1[J].PLo S One,2013,8(8):e71449.
[35]Yang G,Goltsov AA,Ren C,et al.Caveolin-1 Upregulation Contributes to c-Myc-Induced High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer[J].Mol Cancer Res,2012,10(2):218-229.
[36]De Wever J,Frérart F,Bouzin C,et al.Caveolin-1 is critical for the maturation of tumor blood vessels through the regulation of both endothelial tube formation and mural cell recruitment[J].Am J Pathol,2007,171(5):1619-1628.
[37]Núez-Wehinger S,Ortiz RJ,Díaz N,et al.Caveolin-1 in cell migration and metastasis[J].Curr Mol Med,2014,14(2):255-274.
[38]Tahir SA,Park S,Thompson TC.Caveolin-1 regulates VEGF-stimulated angiogenic activities in prostate cancer and endothelial cells[J].Cancer Biol Ther,2009,8(23):2286-2296.
[39]Tahir SA,Yang G,Goltsov AA,et al.Tumor Cell-Secreted Caveolin-1 Has Proangiogenic Activities in Prostate Cancer[J].Cancer Res,2008,68(3):731-739.
[2]Couet J,Belanger MM,Roussel E,et al.Cell biology of caveolae and caveolin[J].Adv Drug Deliv Rev,2001,49(3):223-235.
[3]Couet J,Li S,Okamoto T,et al.Identification of peptide and protein ligands for the Caveolin-scaffolding domain.Implications for the interaction of Caveolin with Caveolaeassociated proteins[J].J Biol Chem,1997,272(10):6525-6533.
[4]Mercier I,Jasmin JF,Pavlides S,et al.Clinical and translational implications of the caveolin gene family:lessons from mouse models and human genetic disorders[J].Lab Invest,2009,89(6):614-623.
[5]Senetta R,Stella G,Pozzi E,et al.Caveolin-1 as a promoter of tumour spreading:when,how,where and why[J].J Cell Mol Med,2013,17(3):325-336.
[6]Qin H1,Bollag WB.The caveolin-1 scaffolding domain peptide decreases phosphatidylglycerol levels and inhibits calcium-induced differentiation in mouse keratinocytes[J].PLo S One,2013,8(11):e80946.
[7]Han H,Rosenhouse-Dantsker A,Gnanasambandam R,et al.Silencing of Kir2 channels by caveolin-1:crosstalk with cholesterol[J].J Physiol,2014,592(Pt 18):4025-4038.
[8]Swrd K,Albinsson S,Rippe C.Arterial dysfunction but maintained systemic blood pressure in cavin-1-deficient mice[J].PLo S One,2014,9(3):e92428.
[9]Pavlides S,Gutierrez-Pajares JL,Katiyar S,et al.Caveolin-1 regulates the anti-atherogenic properties of macrophages[J].Cell Tissue Res,2014,358(3):821-831.
[10]Sato M,Hutchinson DS,Halls ML,et al.Interaction with caveolin-1 modulates G protein coupling of mouseβ3-adrenoceptor[J].J Biol Chem,2012,287(24):20674-20688.
[11]郭贵明,吕智.Caveolin-1在肿瘤中的研究进展[J].实用骨科杂志,2009,15(1):33-35,73.
[12]Shen XJ,Zhang H,Tang GS,et al.Caveolin-1 is a Modulator of Fibroblast Activation and a Potential Biomarker for Gastric Cancer[J].Int J Biol Sci,2015,11(4):370-379.
[13]Ma W,Wang DD,Li L,et al.Caveolin-1 plays a key role in the oleanolic acid-induced apoptosis of HL-60cells[J].Oncol Rep,2014,32(1):293-301.
[14]Friedrich T,Richter B,Gaiser T,et al.Deficiency of caveolin-1 in Apc(min/+)mice promotes colorectal tumorigenesis[J].Carcinogenesis,2013,34(9):2109-2118.
[15]Xu J,Agyemang S,Qin Y,et al.A Novel Pathway that Links Caveolin-1 Down-Regulation to BRCA1 Dysfunction in Serous Epithelial Ovarian Cancer Cells[J].Enliven Chall Cancer Detect Ther,2014,1(1).pii:004.
[16]Simpkins SA,Hanby AM,Holliday DL,et al.Clinical and functional significance of loss of caveolin-1 expression in breast cancer-associated fibroblasts[J].JPathol,2012,227(4):490-498.
[17]张志波,何庆良,石铮,等.Caveolin-1在肝细胞癌表达及与肿瘤血管生成的关系[J].中国普通外科杂志,2012,21(1):53-57.
[18]Huang C,Qiu Z,Wang L,et al.A novel Fox M1-caveolin signaling pathway promotes pancreatic cancer invasion and metastasis[J].Cancer Res,2012,72(3):655-665.
[19]Li L,Ren C,Yang G,et al.Caveolin-1 promotes autoregulatory,Akt-mediated induction of cancer-promoting growth factors in prostatecancer cells[J].Mol Cancer Res,2009,7(11):1781-1791.
[20]Pancotti F,Roncuzzi L,Maggiolini M,et al.Caveolin-1silencing arrests the proliferation of metastatic lung cancer cells through the inhibition of STAT3 signaling[J].Cell Signal,2012,24(7):1390-1397.
[21]Masuelli L,Budillon A,Marzocchella L,et al.Caveolin-1overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-βcatenins complex and multiple Erb B receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas[J].J Cell Physiol,2012,227(9):3344-3353.
[22]Steffens S,Schrader AJ,Blasig H,et al.Caveolin 1 protein expression in renal cell carcinoma predicts survival[J].BMC Urol,2011,7(11):25.
[23]Bonuccelli G,Casimiro M C,Sotgia F,et al.Caveolin-1(P132L),a common breast cancer mutation,confers mammary cell invasiveness and defines a novel stem cell/metastasis-associated gene signature[J].Am J Pathol,2009,174(5):1650-1662.
[24]袁碧英,易斌,鲁开智,等.Caveolin-1在肿瘤中的作用机制的研究进展[J].中国医学创新,2014,11(6):129-131.
[25]Gratton JP,Lin MI,Yu J,et al.Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice[J].Cancer Cell,2003,4(1):31-39.
[26]Bocci G,Fioravanti A,Orlandi P,et al.Metronomic ceramide analogs inhibit angiogenesis in pancreatic cancer through up-regulation of caveolin-1 and thrombospondin-1 and down-regulation of cyclin D1[J].Neoplasia,2012,14(9):833-845.
[27]Fang K,Fu W,Beardsley AR,et al.Overexpression of caveolin-1 Inhibits endothelial cell proliferation by arresting the Cell Cycle at G[J].Cell Cycle,2007,6(2):199-204.
[28]Ayala G,Morello M,Frolov A,et al.Loss of caveolin-1 in prostate cancer stroma correlates with reduced relapse-free survival and is functionally relevant to tumour progression[J].J Pathol,2013,231(1):77-87.
[29]Philip M.Bauer,Jun Yu,Yan Chen,et al.Endothelialspecific expression of caveolin-1 impairs microvascular permeability and angiogenesis[J].PNAS,2005,102(1):204-209.
[30]Zulli A,Buxton BF,Black MJ,et al.The immunoquantification of caveolin-1 and e NOS in human and rabbit diseased blood vessels[J].J Histochem Cytochem,2006,54(2):151-159.
[31]Brouet A,Dewever J,Martinive P,et al.Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide[J].FASEBJ,2005,19(6):602-604.
[32]Zhang ZB,Cai L,Zheng SG,et al.Overexpression of caveolin-1 in hepatocellular carcinoma with metastasis and worse prognosis:correlation with vascular endothelial growth factor,microvessel density and unpaired artery[J].Pathol Oncol Res,2009,15(3):495-502.
[33]Nassar ZD,Moon H,Duong T,et al.PTRF/Cavin-1decreases prostate cancer angiogenesis and lymphangiogenesis[J].Oncotarget,2013,4(10):1844-1855.
[34]Sáinz-Jaspeado M,Huertas-Martinez J,Lagares-Tena L,et al.Eph A2-induced angiogenesis in ewing sarcoma cells works through b FGF production and is dependent on caveolin-1[J].PLo S One,2013,8(8):e71449.
[35]Yang G,Goltsov AA,Ren C,et al.Caveolin-1 Upregulation Contributes to c-Myc-Induced High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer[J].Mol Cancer Res,2012,10(2):218-229.
[36]De Wever J,Frérart F,Bouzin C,et al.Caveolin-1 is critical for the maturation of tumor blood vessels through the regulation of both endothelial tube formation and mural cell recruitment[J].Am J Pathol,2007,171(5):1619-1628.
[37]Núez-Wehinger S,Ortiz RJ,Díaz N,et al.Caveolin-1 in cell migration and metastasis[J].Curr Mol Med,2014,14(2):255-274.
[38]Tahir SA,Park S,Thompson TC.Caveolin-1 regulates VEGF-stimulated angiogenic activities in prostate cancer and endothelial cells[J].Cancer Biol Ther,2009,8(23):2286-2296.
[39]Tahir SA,Yang G,Goltsov AA,et al.Tumor Cell-Secreted Caveolin-1 Has Proangiogenic Activities in Prostate Cancer[J].Cancer Res,2008,68(3):731-739.