|
胶原蛋白在胰腺癌中的研究进展
|
Abstract:
胶原蛋白(collagen)是一个广泛分布于全身的三螺旋蛋白大家族,是由三条α肽链构成的三聚螺旋体结构。可以根据它们的共同结构域、同源性和功能分为七类,分别是:纤维性胶原、网状胶原蛋白、FACITs (fibril-associated collagens with interrupted triple helices)、MACITs (三螺旋中断的膜相关胶原)、锚定纤维、珠丝形成胶原蛋白、MULTIPLEXIN (多个三螺旋结构域和中断)/产生内皮抑素的胶原蛋白。近年来有关研究发现,胶原蛋白由促结缔组织基质内的胰腺星状细胞(Pancreatic stellate cells, PSC)产生并促进胰腺癌(pancreatic cancer, PC)细胞粘附、增殖、迁移和化学抗性。但也有大量研究发现有高基质含量的患者生存率反而更高;去除癌相关成纤维细胞(Cancer-associated fibroblasts, CAFs)基因的患癌小鼠生存率更低;I型胶原蛋白的缺失会加速胰腺癌的进展。以上研究证实了,胰腺癌的间质成分可能通过复杂的机制影响着胰腺癌的发生发展。并且与胰腺癌的发生发展密切相关。本文简要总结与胰腺癌相关的胶原蛋白以及它们之间的关系,包括IV型、VI型、X型胶原蛋白,并有望成为胰腺癌的肿瘤标志物以及为胰腺癌的诊断及治疗提供初步的理论依据。
Collagen is a large family of triple helix proteins widely distributed throughout the body, and is a triple helix structure composed of three α-peptide chains. It can be divided into seven categories according to their common domains, homology and function, namely: fibrillar collagens, reticular collagens, FACITs (fibril-associated collagens with interrupted triple helices), MACITs (membrane-associated triple helices interrupted collagen), anchoring fibers, bead-forming collagen, MULTIPLEXIN (multiple triple helical domains and interruptions)/endostatin-producing collagen. Recent studies have found that collagen is produced by pancreatic stellate cells (PSC) in the connective tissue matrix and promotes cell adhesion, proliferation, migration and chemoresistance in pancreatic cancer (PC). However, a large number of studies have also found that patients with high stromal content have a higher survival rate; the survival rate of mice of cancer-associated fibroblasts (CAFs) gene deletion is lower; the loss of type I collagen will accelerate pancreatic cancer progression. The above studies have confirmed that the interstitial components of pancreatic cancer may affect the occurrence and development of pancreatic cancer through complex mechanisms. And it is closely related to the occurrence and development of pancreatic cancer. This article briefly summarizes the collagens related to pancreatic cancer and the relationship between them, including type IV, type VI, and type X collagen, which are expected to become tumor markers of pancreatic cancer and provide a preliminary theory for the diagnosis and treatment of pancreatic cancer.
[1] | Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424. https://doi.org/10.3322/caac.21492 |
[2] | Siegel, R.L., Miller, K.D. and Jemal, A. (2020) Cancer Statistics, 2020. CA: A Cancer Journal for Clinicians, 70, 7-30.
https://doi.org/10.3322/caac.21590 |
[3] | Siegel, R.L., Miller, K.D. and Jemal, A. (2019) Cancer Statistics, 2019. CA: A Cancer Journal for Clinicians, 69, 7-34.
https://doi.org/10.3322/caac.21551 |
[4] | Rahib, L., Smith, B.D., Aizenberg, R., Rosenzweig, A.B., Fleshman, J.M. and Matrisian, L.M. (2014) Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States. Cancer Research, 74, 2913-2921. https://doi.org/10.1158/0008-5472.CAN-14-0155 |
[5] | Sun, D., Cao, M., Li, H., et al. (2020) Cancer Burden and Trends in China: A Review and Comparison with Japan and South Korea. Chinese Journal of Cancer Research, 32, 129-139. https://doi.org/10.21147/j.issn.1000-9604.2020.02.01 |
[6] | 杨程显, 李戈, 张立颖. 胶原蛋白IV在肿瘤领域的研究进展[J]. 重庆医学, 2015, 44(32): 4586-4589. |
[7] | 许婷, 杨明夏. 胶原蛋白VI在肿瘤中的作用研究进展[J]. 中国现代医学杂志, 2020, 30(14): 47-52. |
[8] | 周炜建, 刘超英. X型胶原蛋白在恶性肿瘤中的研究进展[J]. 现代肿瘤医学, 2020, 28(16): 2898-2901. |
[9] | Nissen, N.I., Karsdal, M. and Willumsen, N. (2019) Collagens and Cancer Associated Fibroblasts in the Reactive Stroma and Its Relation to Cancer Biology. Journal of Experimental & Clinical Cancer Research, 38, Article No. 115.
https://doi.org/10.1186/s13046-019-1110-6 |
[10] | Shoulders, M.D. and Raines, R.T. (2009) Collagen Structure and Stability. Annual Review of Biochemistry, 78, 929-958. https://doi.org/10.1146/annurev.biochem.77.032207.120833 |
[11] | Kadler, K.E., Baldock, C., Bella, J. and Boot-Handford, R.P. (2007) Collagens at a Glance. Journal of Cell Science, 120, 1955-1958. https://doi.org/10.1242/jcs.03453 |
[12] | Provenzano, P.P., Cuevas, C., Chang, A.E., Goel, V.K., Von Hoff, D.D. and Hingorani, S.R. (2012) Enzymatic Targeting of the Stroma Ablates Physical Barriers to Treatment of Pancreatic Ductal Adenocarcinoma. Cancer Cell, 21, 418-429. https://doi.org/10.1016/j.ccr.2012.01.007 |
[13] | Dangi-Garimella, S., Sahai, V., Ebine, K., Kumar, K. and Munshi, H.G. (2013) Three-Dimensional Collagen I Promotes Gemcitabine Resistance in Vitro in Pancreatic Cancer Cells through HMGA2-Dependent Histone Acetyltransferase Expression. PLoS ONE, 8, e64566. https://doi.org/10.1371/journal.pone.0064566 |
[14] | Shields, M.A., Dangi-Garimella, S., Redig, A.J., et al. (2012) Biochemical Role of the Collagen-Rich Tumour Microenvironment in Pancreatic Cancer Progression. Biochemical Journal, 441, 541-552.
https://doi.org/10.1042/BJ20111240 |
[15] | Hamada, S. and Masamune, A. (2018) Elucidating the Link between Collagen and Pancreatic Cancer: What’s Next? Expert Review of Gastroenterology & Hepatology, 12, 315-317. https://doi.org/10.1080/17474124.2018.1448268 |
[16] | Duan, W., Ma, J., Ma, Q., Xu, Q., Lei, J., Han, L., Li, X., Wang, Z., Wu, Z., Lv, S., Ma, Z., Liu, M., Wang, F. and Wu, E. (2014) The Activation of Beta1-Integrin by Type I Collagen Coupling with the Hedgehog Pathway Promotes the Epithelial- Mesenchymal Transition in Pancreatic Cancer. Current Cancer Drug Targets, 14, 446-457.
https://doi.org/10.2174/1568009614666140402105101 |
[17] | Huang, H., Svoboda, R.A., Lazenby, A.J., Saowapa, J., Chaika, N., Ding, K., Wheelock, M.J. and Johnson, K.R. (2016) Up-Regulation of N-Cadherin by Collagen I-Activated Discoidin Domain Receptor 1 in Pancreatic Cancer Requires the Adaptor Molecule Shc1. Journal of Biological Chemistry, 291, 23208-23223.
https://doi.org/10.1074/jbc.M116.740605 |
[18] | Torphy, R.J., Wang, Z., True-Yasaki, A., Volmar, K.E., Rashid, N., Yeh, B., Anderson, J.M., Johansen, J.S., Hollingsworth, M.A., Yeh, J.J. and Collisson, E.A. (2018) Stromal Content Is Correlated with Tissue Site, Contrast Retention, and Survival in Pancreatic Adenocarcinoma. JCO Precision Oncology, 17, Article ID: 00121.
https://doi.org/10.1200/PO.17.00121 |
[19] | ?zdemir, B.C., Pentcheva-Hoang, T., Carstens, J.L., et al. (2014) Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival. Cancer Cell, 25, 719-734. https://doi.org/10.1016/j.ccr.2014.04.005 |
[20] | Madsen, C.D. (2021) Pancreatic Cancer Is Suppressed by Fibroblast-Derived Collagen I. Cancer Cell, 39, 451-453.
https://doi.org/10.1016/j.ccell.2021.02.017 |
[21] | Daniel, ?., Oskar, F., Erik, L., et al. (2013) Type IV Collagen Stimulates Pancreatic Cancer Cell Proliferation, Migration, and Inhibits Apoptosis through an Autocrine Loop. BMC Cancer, 13, Article No. 154.
https://doi.org/10.1186/1471-2407-13-154 |
[22] | Ohlund, D., Lundin, C., Ardnor, B., et al. (2009) Type IV Collagen Is a Tumour Stroma-Derived Biomarker for Pancreas Cancer. British Journal of Cancer, 101, 91-97. https://doi.org/10.1038/sj.bjc.6605107 |
[23] | 张元, 曹庆飞, 佟明. COL6A1高表达对肾透明细胞癌患者预后的影响[J]. 锦州医科大学学报, 2021, 42(3): 56-63. |
[24] | 陈佳琦. COL6A3在肾癌中的表达及临床意义[D]: [硕士学位论文]. 长春: 吉林大学, 2021. |
[25] | 张竞, 谢扬, 王凤, 齐健. COL6A3基因与胃癌免疫浸润水平及临床预后的相关性分析[J]. 消化肿瘤杂志(电子版), 2020, 12(4): 248-255. |
[26] | 郑多安, 郑漫漫, 孟翔凌, 孙登群, 孙艳军, 陈晓玲. COL6A2基因在胃癌中的表达及临床意义[J]. 武警医学, 2020, 31(9): 765-770. |
[27] | 谢春英. COL6A3在结直肠癌中的表达及相关临床意义[D]: [硕士学位论文]. 长春: 吉林大学, 2018. |
[28] | 王芃芃. Collagen VI在喉癌中筛查、鉴定及迁移粘附分子机制的研究[D]: [博士学位论文]. 沈阳: 中国医科大学, 2019. |
[29] | 杨荣权, 廖泽明, 蔡勇, 王超. 抑制COL6A1基因表达对膀胱癌T24细胞增殖和侵袭能力的影响[J]. 临床泌尿外科杂志, 2019, 34(6): 449-452+458. |
[30] | Karamitopoulou, E. (2013) Role of Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Is Tumor Budding the Missing Link? Frontiers in Oncology, 3, Article No. 221. https://doi.org/10.3389/fonc.2013.00221 |
[31] | Handra-Luca, A., Hong, S.M., Walter, K., et al. (2011) Tumour Epithelial Vimentin Expression and Outcome of Pancreatic Ductal Adenocarcinomas. British Journal of Cancer, 104, 1296-1302. https://doi.org/10.1038/bjc.2011.93 |
[32] | Kang, C.Y., Wang, J., Axell-House, D., et al. (2014) Clinical Significance of Serum COL6A3 in Pancreatic Ductal Adenocarcinoma. Journal of Gastrointestinal Surgery, 18, 7-15. https://doi.org/10.1007/s11605-013-2326-y |
[33] | Owusu-Ansah Kwabena Gyabaah. COL6A1促进胰腺癌转移及临床意义研究[D]: [博士学位论文]. 杭州: 浙江大学, 2019. |
[34] | Chan, D. and Jacenko, O. (1998) Phenotypic and Biochemical Consequences of Collagen X Mutations in Mice and Humans. Matrix Biology, 17, 169-184. https://doi.org/10.1016/S0945-053X(98)90056-7 |
[35] | Chen, Q.A., Gibney, E., Fitch, J.M., et al. (1990) Long-Range Movement and Fibril Association of Type X Collagen within Embryonic Cartilage Matrix. Proceedings of the National Academy of Sciences of the United States of America, 87, 8046-8050. https://doi.org/10.1073/pnas.87.20.8046 |
[36] | Jacenko, O., LuValle, P.A. and Olsen, B.R. (1993) Spondylometaphyseal Dysplasia in Mice Carrying a Dominant Negative Mutation in a Matrix Protein Specific for Cartilage-to-Bone Transition. Nature, 365, 56-61.
https://doi.org/10.1038/365056a0 |
[37] | Chung, K.S., Jacenko, O., Boyle, P., et al. (1997) Craniofacial Abnormalities in Mice Carrying a Dominant Interference Mutation in Type X Collagen. Developmental Dynamics, 208, 544-552.
https://doi.org/10.1002/(SICI)1097-0177(199704)208:4%3C544::AID-AJA10%3E3.0.CO;2-X |
[38] | Dublet, B., Venet, T. and van der Rest, M. (1999) Schmid’s Metaphyseal Chondrodysplasia Mutations Interfere with Folding of the C-Terminal Domain of Human Collagen X Expressed in Escherichia coli. Journal of Biological Chemistry, 274, 18909-18915. https://doi.org/10.1074/jbc.274.27.18909 |
[39] | 陈况, 柳俨哲, 胡明根. X 型胶原蛋白在胰腺癌中的表达及与胰腺癌预后的关系[J]. 解放军医学院报, 2019, 40(4): 373-376+394. |