胰岛素样生长因子1受体在胰腺癌治疗中的机制及进展
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摘要
胰岛素样生长因子(IGF)1受体(IGF-1R)广泛存在于多种类型的细胞表面,与肿瘤细胞的形成、发展密切相关,也为肿瘤的靶向治疗提供了新的方向。对IGF-1R在胰腺癌中的表达、发生、发展以及IGF-1R作为靶点治疗肿瘤的进展作一综述。
Insulin-like growth factor-1 receptor( IGF-1R) widely exists in the surface of various types of cells and is closely associated with the formation and development of tumor cells. It also provides a new direction for the targeted therapy for tumors. This article reviews the expression,development,and progression of IGF-1R in pancreatic cancer and research advances in IGF-1R as a target for tumor treatment.
Insulin-like growth factor-1 receptor( IGF-1R) widely exists in the surface of various types of cells and is closely associated with the formation and development of tumor cells. It also provides a new direction for the targeted therapy for tumors. This article reviews the expression,development,and progression of IGF-1R in pancreatic cancer and research advances in IGF-1R as a target for tumor treatment.
引文
[1]DAI B,WANG DS,ZHANG Y,et al.Research advances in the role of insulin-like growth factors in tumor[J/CD].Chin J Clinicians:Electronic Edition,2013,7(15):7099-7102.(in Chinese)戴斌,王德盛,张勇,等.胰岛素样生长因子家族在肿瘤中的作用研究进展[J/CD].中华临床医师杂志:电子版,2013,7(15):7099-7102.
[2]OUBAN A,MURACA P,YEATMAN T,et al.Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas[J].Hum Pathol,2003,34(8):803-808.
[3]JANEWAY KA,ZHU MJ,BARRETINA J,et al.Strong expression of IGF-1R in pediatric gastrointestinal stromal tumors without IGF-1R genomic amplification[J].Int J Cancer,2010,127(11):2718-2722.
[4]HAISA M.The type 1 insulin-like growth factor receptor signalling system and targeted tyrosine kinase inhibition in cancer[J].J Int Med Res,2013,41(2):253-264.
[5]CAO YH,XU CF.Insulin-like growth factor type 1 receptor and malignancy:an update[J].J Mod Oncol,2015,23(5):706-709.(in Chinese)曹友红,许春芳.胰岛素样生长因子-1受体在恶性肿瘤中的研究进展[J].现代肿瘤医学,2015,23(5):706-709.
[6]ADAMS TE,EPA VC,GARRETT TPJ,et al.Structure and function of the type 1 insulin-like growth factor receptor[J].Cell Mol Life Sci,2000,57(7):1050-1093.
[7]KING ER,WONG KK.Insulin-like growth factor:current concepts and new developments in cancer therapy[J].Recent Pat Anticancer Drug Discw,2012,7(1):14-30.
[8]CHAKRABORTY AK,WELSH A,DIGIOVANNA MP.Co-targeting the insulin-like growth factor 1 receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer celllines[J].Breast Cancer Res Treat,2010,120(2):327-335.
[9]MATSUDA Y,ICHIDA T.Impact of hepatitis B virus X protein on the DNA damage response during hepatocarcinogenesis[J].Med Mol Morphol,2009,42(3):138-142.
[10]KIM YH,SUMIYOSHI S,HASHIMOTO S,et al.Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer[J].Clin Lung Cancer,2012,13(5):385-390.
[11]YAMAMOTO T,OSHIMA T,YOSHIHARA K,et al.Clinical significance of immunohistochemical expression of insulin-like growth factor-1 receptor and matrix metalloproteinase-7 in resected non-small cell lung cancer[J].Exp Ther Med,2012,3(5):797-802.
[12]RYAN CJ,HAQQ CM,SIMKO J,et al.Expression of insulin-like growth faetor-I receptor in local and metastatic prostate cancer[J].Urol Oncol,2007,25(2):134-140.
[13]LUO M,SHEN DX,ZHOU XN,et al.MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor[J].Surgery,2013,153(6):836-847.
[14]PAN C,YANG SY,YIN SH,et al.Heat shock protein 90αand Insulin-like growth factor-1 receptor(IGF-1R)on expression level and clinicopathologic data in pancreatic cancer[J].Zhejiang Clin Med J,2015,17(10):1663-1665.(in Chinese)潘超,杨世勇,殷少华,等.HSP90α和IGF-1R在胰腺癌组织中的表达及临床意义[J].浙江临床医学,2015,17(10):1663-1665.
[15]LI H,LI J,LIU X.et al.Effect of PTEN and KAll gene overexpression on the proliferation,metastasis and radiosensitivity of ASPC1pancreatic cancer cells under hypoxic conditions[J].Mol Med Rep,2014,10(4):1973-1977.
[16]AMSTERDAM A,SHPIGNER L,RAANAN C,et al.Dynarmc distribution of ERK,p38 and JNK during the development of pancreatic ductal adenocarcinoma[J].Aeta Histochem,2014,116(8):1434-1442.
[17]REDLAK MJ,MILLER TA.Targeting PI3K/Akt/HSP90 signaling sensitizes gastric cancer cells to deoxycholate-induced apoptosis[J].Dig Dis Sci,2011,56(2):323-329.
[18]BREINIG M,MAYER P,HARJUNG A,et al.Heat shock protein90-sheltered overexpression of insulin-like growth factor 1 receptor contributes to malignancy of thymic epithelial tumors[J].Clin Cancer Res,2011,17(8):2237-2249.
[19]XU W,NECKERS L.Targeting the molecular chaperone heat shock protein 90 provides a multifaceted effect on diverse cell signaling pathways of cancer cells[J].Clin Cancer Res,2007,13(6):1625-1629.
[20]XU JW,WANG TX,YOU L,et al.Insulin-like growth factor 1receptor(IGF-1R)as a target of MiR-497 and plasma IGF-1R levels associated with TNM stage of pancreatic cancer[J].PLo S One,2014,9(3):e92847.
[21]STOEHZING O,LIU W,REINMUTH N,et al.Regulation of hypoxia inducible factor-1 alpha,vascular endothelial growth factor,and angiogenesis by an insulin-like factor 1 receptor autocrine loop in human pancreatic cancer[J].Am J Pathol,2003,163(3):1001-1011.
[22]HUANG PZ,HE T.Expression of IGF-1R,VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma[J].Eur J Gynaecol Oncol,2011,32(6):660-664.
[23]TANG YC,ZHANG DL,FALLAVOLLITA L,et al.Vascular endothelial growth factor C expression and lymph nodc metastasis are regula Ied by the type 1 insulin-like growth factor receptor[J].Cancer Res,2003,63(6):1166-1171.
[24]LEE CT,PARK KH,ADACHI Y,et al.Recombinant adenoviruses expressing dominant negative insulin-like growth factor-1 receptor demonstrate antitumor effects on lung cancer[J].Cancer Gene Ther,2003,10(1):57-63.
[25]HARTOG H,WESSCLING J,BOEZEN HM,et al.The insulinlike growth factor l receptor in cancer old focus,new future[J].Eur J Cancer,2007,43:1895-1904.
[26]STOELTZING O,LIU W,REINMUTH N,et al.Regulation of hipoxia-inducibal factor-1alpha,vascular endothelial growth factor and angiogenesis by a insulin-like growth factor-l receptor in autocrine loop in human pancreatic cancer[J].Am J Panthol,2003,163(3):1001-1011.
[27]Mc KINLEY ET,BUGAJ JE,ZHAO P,et al.18FDG-PET predicts pharmacodynamic response to OSI-906,a Dual IGF-1R/IR inhibitor,inpreclinical mouse models of lung cancer[J].Clin Cancer Res,2011,17(10):3332-3340.
[28]ZHAO H,DESAI V,WANG J,et al.Epithelial-mesenchyma transition predicts sensitivity to the duaf IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma cell lines[J].Mol Cancer Ther,2012,11(2):503-513.
[29]HALUSKA P,CARBONI JM,LOEGERING DA,et al.In vitro and in vivo antitumor effects of the dual in sulin-like growth factor-1/insulin receptor inhibitor,BMS-554417[J].Anti Cancer Res,2006,66(28):362-371.
[30]MULVIHILL MJ,COOKE A,ROSENFEL-FRANKLIN M,et al.Discovery of OSI-906:a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor[J].Future Med Chem,2009,1(6):1153-1171.
[31]ZHOU H,RAO J,LIN J,et al.The insulin-like growth factor-1 receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastomato the effects of chemotherapy[J].Oncol Rep,2011,25(6):1565-1571.
[32]YEH J,LITZ J,HAUCK P,et al.Selective inhibition of SCLC growth by the A12 anti-IGF-1R monaclonal antibody correlates with inhibition of Akt[J].Lung Cancer,2008,60(2):166-174.
[33]WEST HJ.Novel targeted agents for lung cancer[J].Clin Lung Cancer,2009,10(1):41-46.
[34]SHIN DH,MIN HY,EL-NAGGAR AK,et al.Akt/m TOR counteract the antitumor activities of cixutumumab,an anti-insulinlike growth factor I receptor monoclonal antibody[J].Mol Cancer Ther,2011,10(12):2437-2448.
[35]ATTIAS-GEVA Z,BENTOV I,LUDWIG DL,et al.Insulinlike growth factor-I receptor(IGF-IR)targeting with monoclona I antibody cixutumumab(1MC-A12)inhibits IGF-1action in endonletria I cancer cells[J].Eur J Cancer,2011,47(11):1717-1726.
[36]MENDIVIF A,ZHOU C,CANTRELL LA,et a I.AMG 479,a novel l GF-1R antibody,inhibits endometrial cancer cell proliferation through disruption of the PI3K/Akt and MAPK pathways[J].Reprod Sci,2011,18(9):832-841.
[37]ZAMECNIK PC,STEPHENSON ML.Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynuclleotide[J].Proc Natl Acad Sci USA,1978,75(1):280-284.
[38]PAN YZ,SUN CY,WANG YZ.Growth inhibition of human pancreatic cancer cells by lipofection mediated IGF-1R antisense oligodeoxynucletides in combination with ionizing radiation[J].Chin J Radiological Med Prot,2003,24(2):114-116.(in Chinese)潘耀振,孙诚谊,王玉芝.脂质体介导的IGF-1R反义寡核苷酸对胰腺癌细胞生长的抑制作用[J].中华放射医学与防护杂志,2003,24(2):114-116.
[39]WANG ZY.The anticancer research of antisense oligonucleotides targeting insulin-like growth factor 1 receptor[D].Beijing:Inst Radiat Med,China Acad Mil Med Sci,2006:1-70.(in Chinese)王芝艳.靶向胰岛素样生长因子1型受体的反义寡核苷酸抗肿瘤治疗[D].北京:军事医学科学院放射与辐射医学研究所,2006:1-70.
[40]BAI S,NASSER MW,WANG B,et al.MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib[J].J Biol Chem,2009,284(46):32015-32027.
[2]OUBAN A,MURACA P,YEATMAN T,et al.Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas[J].Hum Pathol,2003,34(8):803-808.
[3]JANEWAY KA,ZHU MJ,BARRETINA J,et al.Strong expression of IGF-1R in pediatric gastrointestinal stromal tumors without IGF-1R genomic amplification[J].Int J Cancer,2010,127(11):2718-2722.
[4]HAISA M.The type 1 insulin-like growth factor receptor signalling system and targeted tyrosine kinase inhibition in cancer[J].J Int Med Res,2013,41(2):253-264.
[5]CAO YH,XU CF.Insulin-like growth factor type 1 receptor and malignancy:an update[J].J Mod Oncol,2015,23(5):706-709.(in Chinese)曹友红,许春芳.胰岛素样生长因子-1受体在恶性肿瘤中的研究进展[J].现代肿瘤医学,2015,23(5):706-709.
[6]ADAMS TE,EPA VC,GARRETT TPJ,et al.Structure and function of the type 1 insulin-like growth factor receptor[J].Cell Mol Life Sci,2000,57(7):1050-1093.
[7]KING ER,WONG KK.Insulin-like growth factor:current concepts and new developments in cancer therapy[J].Recent Pat Anticancer Drug Discw,2012,7(1):14-30.
[8]CHAKRABORTY AK,WELSH A,DIGIOVANNA MP.Co-targeting the insulin-like growth factor 1 receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer celllines[J].Breast Cancer Res Treat,2010,120(2):327-335.
[9]MATSUDA Y,ICHIDA T.Impact of hepatitis B virus X protein on the DNA damage response during hepatocarcinogenesis[J].Med Mol Morphol,2009,42(3):138-142.
[10]KIM YH,SUMIYOSHI S,HASHIMOTO S,et al.Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer[J].Clin Lung Cancer,2012,13(5):385-390.
[11]YAMAMOTO T,OSHIMA T,YOSHIHARA K,et al.Clinical significance of immunohistochemical expression of insulin-like growth factor-1 receptor and matrix metalloproteinase-7 in resected non-small cell lung cancer[J].Exp Ther Med,2012,3(5):797-802.
[12]RYAN CJ,HAQQ CM,SIMKO J,et al.Expression of insulin-like growth faetor-I receptor in local and metastatic prostate cancer[J].Urol Oncol,2007,25(2):134-140.
[13]LUO M,SHEN DX,ZHOU XN,et al.MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor[J].Surgery,2013,153(6):836-847.
[14]PAN C,YANG SY,YIN SH,et al.Heat shock protein 90αand Insulin-like growth factor-1 receptor(IGF-1R)on expression level and clinicopathologic data in pancreatic cancer[J].Zhejiang Clin Med J,2015,17(10):1663-1665.(in Chinese)潘超,杨世勇,殷少华,等.HSP90α和IGF-1R在胰腺癌组织中的表达及临床意义[J].浙江临床医学,2015,17(10):1663-1665.
[15]LI H,LI J,LIU X.et al.Effect of PTEN and KAll gene overexpression on the proliferation,metastasis and radiosensitivity of ASPC1pancreatic cancer cells under hypoxic conditions[J].Mol Med Rep,2014,10(4):1973-1977.
[16]AMSTERDAM A,SHPIGNER L,RAANAN C,et al.Dynarmc distribution of ERK,p38 and JNK during the development of pancreatic ductal adenocarcinoma[J].Aeta Histochem,2014,116(8):1434-1442.
[17]REDLAK MJ,MILLER TA.Targeting PI3K/Akt/HSP90 signaling sensitizes gastric cancer cells to deoxycholate-induced apoptosis[J].Dig Dis Sci,2011,56(2):323-329.
[18]BREINIG M,MAYER P,HARJUNG A,et al.Heat shock protein90-sheltered overexpression of insulin-like growth factor 1 receptor contributes to malignancy of thymic epithelial tumors[J].Clin Cancer Res,2011,17(8):2237-2249.
[19]XU W,NECKERS L.Targeting the molecular chaperone heat shock protein 90 provides a multifaceted effect on diverse cell signaling pathways of cancer cells[J].Clin Cancer Res,2007,13(6):1625-1629.
[20]XU JW,WANG TX,YOU L,et al.Insulin-like growth factor 1receptor(IGF-1R)as a target of MiR-497 and plasma IGF-1R levels associated with TNM stage of pancreatic cancer[J].PLo S One,2014,9(3):e92847.
[21]STOEHZING O,LIU W,REINMUTH N,et al.Regulation of hypoxia inducible factor-1 alpha,vascular endothelial growth factor,and angiogenesis by an insulin-like factor 1 receptor autocrine loop in human pancreatic cancer[J].Am J Pathol,2003,163(3):1001-1011.
[22]HUANG PZ,HE T.Expression of IGF-1R,VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma[J].Eur J Gynaecol Oncol,2011,32(6):660-664.
[23]TANG YC,ZHANG DL,FALLAVOLLITA L,et al.Vascular endothelial growth factor C expression and lymph nodc metastasis are regula Ied by the type 1 insulin-like growth factor receptor[J].Cancer Res,2003,63(6):1166-1171.
[24]LEE CT,PARK KH,ADACHI Y,et al.Recombinant adenoviruses expressing dominant negative insulin-like growth factor-1 receptor demonstrate antitumor effects on lung cancer[J].Cancer Gene Ther,2003,10(1):57-63.
[25]HARTOG H,WESSCLING J,BOEZEN HM,et al.The insulinlike growth factor l receptor in cancer old focus,new future[J].Eur J Cancer,2007,43:1895-1904.
[26]STOELTZING O,LIU W,REINMUTH N,et al.Regulation of hipoxia-inducibal factor-1alpha,vascular endothelial growth factor and angiogenesis by a insulin-like growth factor-l receptor in autocrine loop in human pancreatic cancer[J].Am J Panthol,2003,163(3):1001-1011.
[27]Mc KINLEY ET,BUGAJ JE,ZHAO P,et al.18FDG-PET predicts pharmacodynamic response to OSI-906,a Dual IGF-1R/IR inhibitor,inpreclinical mouse models of lung cancer[J].Clin Cancer Res,2011,17(10):3332-3340.
[28]ZHAO H,DESAI V,WANG J,et al.Epithelial-mesenchyma transition predicts sensitivity to the duaf IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma cell lines[J].Mol Cancer Ther,2012,11(2):503-513.
[29]HALUSKA P,CARBONI JM,LOEGERING DA,et al.In vitro and in vivo antitumor effects of the dual in sulin-like growth factor-1/insulin receptor inhibitor,BMS-554417[J].Anti Cancer Res,2006,66(28):362-371.
[30]MULVIHILL MJ,COOKE A,ROSENFEL-FRANKLIN M,et al.Discovery of OSI-906:a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor[J].Future Med Chem,2009,1(6):1153-1171.
[31]ZHOU H,RAO J,LIN J,et al.The insulin-like growth factor-1 receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastomato the effects of chemotherapy[J].Oncol Rep,2011,25(6):1565-1571.
[32]YEH J,LITZ J,HAUCK P,et al.Selective inhibition of SCLC growth by the A12 anti-IGF-1R monaclonal antibody correlates with inhibition of Akt[J].Lung Cancer,2008,60(2):166-174.
[33]WEST HJ.Novel targeted agents for lung cancer[J].Clin Lung Cancer,2009,10(1):41-46.
[34]SHIN DH,MIN HY,EL-NAGGAR AK,et al.Akt/m TOR counteract the antitumor activities of cixutumumab,an anti-insulinlike growth factor I receptor monoclonal antibody[J].Mol Cancer Ther,2011,10(12):2437-2448.
[35]ATTIAS-GEVA Z,BENTOV I,LUDWIG DL,et al.Insulinlike growth factor-I receptor(IGF-IR)targeting with monoclona I antibody cixutumumab(1MC-A12)inhibits IGF-1action in endonletria I cancer cells[J].Eur J Cancer,2011,47(11):1717-1726.
[36]MENDIVIF A,ZHOU C,CANTRELL LA,et a I.AMG 479,a novel l GF-1R antibody,inhibits endometrial cancer cell proliferation through disruption of the PI3K/Akt and MAPK pathways[J].Reprod Sci,2011,18(9):832-841.
[37]ZAMECNIK PC,STEPHENSON ML.Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynuclleotide[J].Proc Natl Acad Sci USA,1978,75(1):280-284.
[38]PAN YZ,SUN CY,WANG YZ.Growth inhibition of human pancreatic cancer cells by lipofection mediated IGF-1R antisense oligodeoxynucletides in combination with ionizing radiation[J].Chin J Radiological Med Prot,2003,24(2):114-116.(in Chinese)潘耀振,孙诚谊,王玉芝.脂质体介导的IGF-1R反义寡核苷酸对胰腺癌细胞生长的抑制作用[J].中华放射医学与防护杂志,2003,24(2):114-116.
[39]WANG ZY.The anticancer research of antisense oligonucleotides targeting insulin-like growth factor 1 receptor[D].Beijing:Inst Radiat Med,China Acad Mil Med Sci,2006:1-70.(in Chinese)王芝艳.靶向胰岛素样生长因子1型受体的反义寡核苷酸抗肿瘤治疗[D].北京:军事医学科学院放射与辐射医学研究所,2006:1-70.
[40]BAI S,NASSER MW,WANG B,et al.MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib[J].J Biol Chem,2009,284(46):32015-32027.