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Original Article

Role of β1-Integrin in Colorectal Cancer: Case-Control Study

The Ewha Medical Journal 2017;40(2):77-86. Published online: April 28, 2017

Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea.

Corresponding author: Ryung-Ah Lee. Department of Surgery, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea. Tel: 82-2-2650-2861, Fax: 82-2-2644-7984, ralee@ewha.ac.kr
• Received: April 7, 2017   • Accepted: April 18, 2017

Copyright © 2017. Ewha Womans University School of Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Objectives
    In the metastatic process, interactions between circulating tumor cells (CTCs) and the extracellular matrix or surrounding cells are required. β1-integrin may mediate these interactions. The aim of this study was to investigate whether β1-integrin is associated with the detection of CTCs in colorectal cancer.
  • Methods
    We enrolled 30 patients with colorectal cancer (experimental group) and 30 patients with benign diseases (control group). Blood samples were obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and β1-integrin mRNA levels were estimated by using reverse transcription-polymerase chain reaction, and the results were compared between the two groups.
  • Results
    CEA mRNA was detected more frequently in colorectal cancer patients than in control patients (P=0.008). CEA mRNA was significantly reduced after surgery in the colorectal cancer patients (P=0.032). β1-integrin mRNA was detected more in colorectal cancer patients than in the patients with benign diseases (P<0.001). In colorectal cancer patients, expression of β1-integrin mRNA was detected more for advanced-stage cancer than for early-stage cancer (P=0.033) and was significantly decreased after surgery (P<0.001). In addition, expression of β1-integrin mRNA was significantly associated with that of CEA mRNA in colorectal cancer patients (P=0.001).
  • Conclusion
    In conclusion, β1-integrin is a potential prognostic factor following surgical resection in colorectal cancer patients. β1-integrin may be a candidate for use as a marker for early detection of micrometastatic tumor cells and for monitoring the therapeutic response in colorectal cancer patients.

This research was supported by The Korean Society of Coloproctology Boryung Research Grant 2012.

  • 1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
  • 2. Steinert G, Scholch S, Koch M, Weitz J. Biology and significance of circulating and disseminated tumour cells in colorectal cancer. Langenbecks Arch Surg 2012;397:535-542.
  • 3. de Castro-Carpeno J, Belda-Iniesta C, Casado Saenz E, Hernandez Agudo E, Feliu Batlle J, Gonzalez Baron M. EGFR and colon cancer: a clinical view. Clin Transl Oncol 2008;10:6-13.
  • 4. Liu Y, Qian J, Feng JG, Ju HX, Zhu YP, Feng HY, et al. Detection of circulating tumor cells in peripheral blood of colorectal cancer patients without distant organ metastases. Cell Oncol (Dordr) 2013;36:43-53.
  • 5. Barbazan J, Alonso-Alconada L, Muinelo-Romay L, Vieito M, Abalo A, Alonso-Nocelo M, et al. Molecular characterization of circulating tumor cells in human metastatic colorectal cancer. PLoS One 2012;7:e40476.
  • 6. Thorsteinsson M, Jess P. The clinical significance of circulating tumor cells in non-metastatic colorectal cancer: a review. Eur J Surg Oncol 2011;37:459-465.
  • 7. Alunni-Fabbroni M, Sandri MT. Circulating tumour cells in clinical practice: mthods of detection and possible characterization. Methods 2010;50:289-297.
  • 8. Haier J, Nasralla M, Nicolson GL. Cell surface molecules and their prognostic values in assessing colorectal carcinomas. Ann Surg 2000;231:11-24.
  • 9. Jinka R, Kapoor R, Sistla PG, Raj TA, Pande G. Alterations in cell-extracellular matrix interactions during progression of cancers. Int J Cell Biol 2012;2012:219196.
  • 10. Wang JY, Wu CH, Lu CY, Hsieh JS, Wu DC, Huang SY, et al. Molecular detection of circulating tumor cells in the peripheral blood of patients with colorectal cancer using RT-PCR: significance of the prediction of postoperative metastasis. World J Surg 2006;30:1007-1013.
  • 11. Bolocan A, Ion D, Ciocan DN, Paduraru DN. Prognostic and predictive factors in colorectal cancer. Chirurgia (Bucur) 2012;107:555-563.
  • 12. Jiang WQ, Fu FF, Li YX, Wang WB, Wang HH, Jiang HP, et al. Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice. J Zhejiang Univ Sci B 2012;13:663-675.
  • 13. Ashworth TR. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 1869;14:146-149.
  • 14. Raeisossadati R, Farshchian M, Ganji A, Tavassoli A, Velayati A, Dadkhah E, et al. Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients. Int J Colorectal Dis 2011;26:1265-1270.
  • 15. Sastre J, Maestro ML, Puente J, Veganzones S, Alfonso R, Rafael S, et al. Circulating tumor cells in colorectal cancer: correlation with clinical and pathological variables. Ann Oncol 2008;19:935-938.
  • 16. Lu CY, Uen YH, Tsai HL, Chuang SC, Hou MF, Wu DC, et al. Molecular detection of persistent postoperative circulating tumour cells in stages II and III colon cancer patients via multiple blood sampling: prognostic significance of detection for early relapse. Br J Cancer 2011;104:1178-1184.
  • 17. Aggarwal C, Meropol NJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, et al. Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer. Ann Oncol 2013;24:420-428.
  • 18. Wong SC, Chan CM, Ma BB, Hui EP, Ng SS, Lai PB, et al. Clinical significance of cytokeratin 20-positive circulating tumor cells detected by a refined immunomagnetic enrichment assay in colorectal cancer patients. Clin Cancer Res 2009;15:1005-1012.
  • 19. Smirnov DA, Zweitzig DR, Foulk BW, Miller MC, Doyle GV, Pienta KJ, et al. Global gene expression profiling of circulating tumor cells. Cancer Res 2005;65:4993-4997.
  • 20. Sato N, Hayashi N, Imamura Y, Tanaka Y, Kinoshita K, Kurashige J, et al. Usefulness of transcription-reverse transcription concerted reaction method for detecting circulating tumor cells in patients with colorectal cancer. Ann Surg Oncol 2012;19:2060-2065.
  • 21. Wai Wong C, Dye DE, Coombe DR. The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis. Int J Cell Biol 2012;2012:340296.
  • 22. Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, et al. Prospective evaluation of serum tissue inhibitor of metalloproteinase 1 and carbonic anhydrase IX in correlation to circulating tumor cells in patients with metastatic breast cancer. Breast Cancer Res 2011;13:R71.
  • 23. Zieglschmid V, Hollmann C, Mannel J, Albert W, Jaeschke-Melli S, Eckstein B, et al. Tumor-associated gene expression in disseminated tumor cells correlates with disease progression and tumor stage in colorectal cancer. Anticancer Res 2007;27:1823-1832.
  • 24. Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 2010;10:9-22.
  • 25. Rathinam R, Alahari SK. Important role of integrins in the cancer biology. Cancer Metastasis Rev 2010;29:223-237.
  • 26. Millard M, Odde S, Neamati N. Integrin targeted therapeutics. Theranostics 2011;1:154-188.
  • 27. Yu MK, Park J, Jeong YY, Moon WK, Jon S. Integrin-targeting thermally cross-linked superparamagnetic iron oxide nanoparticles for combined cancer imaging and drug delivery. Nanotechnology 2010;21:415102.
  • 28. Park CC, Zhang H, Pallavicini M, Gray JW, Baehner F, Park CJ, et al. Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Res 2006;66:1526-1535.
  • 29. Stoeltzing O, Liu W, Reinmuth N, Fan F, Parry GC, Parikh AA, et al. Inhibition of integrin alpha5beta1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice. Int J Cancer 2003;104:496-503.
  • 30. Nam JM, Chung Y, Hsu HC, Park CC. beta1 integrin targeting to enhance radiation therapy. Int J Radiat Biol 2009;85:923-928.
  • 31. Huang WS, Chen CN, Sze CI, Teng CC. Visfatin induces stromal cell-derived factor-1 expression by β1 integrin signaling in colorectal cancer cells. J Cell Physiol 2013;228:1017-1024.
  • 32. Paschos KA, Canovas D, Bird NC. The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis. Cell Signal 2009;21:665-674.
  • 33. Hsu RY, Chan CH, Spicer JD, Rousseau MC, Giannias B, Rousseau S, et al. LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res 2011;71:1989-1998.
  • 34. Andrews EJ, Wang JH, Winter DC, Laug WE, Redmond HP. Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression. J Surg Res 2001;97:14-19.
  • 35. Carbonell WS, DeLay M, Jahangiri A, Park CC, Aghi MK. β1 integrin targeting potentiates antiangiogenic therapy and inhibits the growth of bevacizumab-resistant glioblastoma. Cancer Res 2013;73:3145-3154.
  • 36. Yang B, Gao J, Rao Z, Shen Q. Clinicopathological and prognostic significance of α5β1-integrin and MMP-14 expressions in colorectal cancer. Neoplasma 2013;60:254-261.
  • 37. Bartolome RA, Barderas R, Torres S, Fernandez-Acenero MJ, Mendes M, Garcia-Foncillas J, et al. Cadherin-17 interacts with α2β1 integrin to regulate cell proliferation and adhesion in colorectal cancer cells causing liver metastasis. Oncogene 2014;33:1658-1669.
  • 38. Wong CS, Cheung MT, Ma BB, Pun Hui E, Chan AC, Chan CK, et al. Isolated tumor cells and circulating CK20 mRNA in pN0 colorectal cancer patients. Int J Surg Pathol 2008;16:119-126.
  • 39. Koyanagi K, Bilchik AJ, Saha S, Turner RR, Wiese D, McCarter M, et al. Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial. Clin Cancer Res 2008;14:7391-7396.
  • 40. Ohlsson L, Hammarstrom ML, Israelsson A, Naslund L, Oberg A, Lindmark G, et al. Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR. Br J Cancer 2006;95:218-225.
Fig. 1

Detection of carcinoembryonic antigen (CEA) by real-time polymerase chain reaction (RT-PCR) in the blood of each group. CEA is detected more frequently in colorectal cancer patients as compared with the controls (P=0.008). In colorectal cancer patients, expression of CEA is significantly decreased after operation (P=0.032). β-actin is an internal control.

emj-40-77-g001.jpg
Fig. 2

Detection of β1-integrin by real-time polymerase chain reaction (RT-PCR) in the blood of each group. β1-integrin is detected more frequently in colorectal cancer patients as compared with the controls (P<0.001). In colorectal cancer patients, expression of β1-integrin is significantly decreased after operation (P<0.001). β-actin is an internal control.

emj-40-77-g002.jpg
Fig. 3

Correlation of β1-integrin & carcinoembryonic antigen (CEA). Expression of β1-integrin is significantly associated with that of CEA. (A) In control group, there is a moderate-positive correlation between β1-integrin and CEA (r=0.446, P=0.014). (B) In preoperative status of experimental group, there is a moderate positive correlation between β1-integrin and CEA (r=0.516, P=0.003). (C) In postoperative status of experimental group, there is a high-positive correlation between β1-integrin and CEA (r=0.935, P<0.001).

emj-40-77-g003.jpg
Table 1

Primers used for amplification

CEA, carcinoembryonic antigen; F, forward; R, reverse.

emj-40-77-i001.jpg
Table 2

Characteristics

*Statistically not significant between experimental and control group.

emj-40-77-i002.jpg
Table 3

Expression of CEA according to the clinicopathologic findings

emj-40-77-i003.jpg
Table 4

Expression of CEA in control and experimental groups

*Expression of carcinoembryonic antigen (CEA) was detected more in experimental group rather than in control group (P=0.008).

Density of CEA was higher in experimental group as compared with the controls (P<0.001).

Expression of CEA was more significantly decreased after operation (P=0.032).

§Density of CEA was significantly decreased after operation (P<0.001).

emj-40-77-i004.jpg
Table 5

Expression of β1-integrin according to the clinicopathologic findings

emj-40-77-i005.jpg
Table 6

Expression of β1-integrin in control and experimental groups

*Expression of β1-integrin was detected more in experimental group rather than in control group (P<0.001).

Density of β1-integrin was higher in experimental group as compared with the controls (P<0.001).

Expression of β1-integrin was more significantly decreased after operation (P<0.001).

§Density of β1-integrin was significantly decreased after operation (P<0.001).

emj-40-77-i006.jpg
Table 7

Correlation of β1-integrin & CEA

CEA, carcinoembryonic antigen.

emj-40-77-i007.jpg

Figure & Data

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      Role of β1-Integrin in Colorectal Cancer: Case-Control Study
      Image Image Image
      Fig. 1 Detection of carcinoembryonic antigen (CEA) by real-time polymerase chain reaction (RT-PCR) in the blood of each group. CEA is detected more frequently in colorectal cancer patients as compared with the controls (P=0.008). In colorectal cancer patients, expression of CEA is significantly decreased after operation (P=0.032). β-actin is an internal control.
      Fig. 2 Detection of β1-integrin by real-time polymerase chain reaction (RT-PCR) in the blood of each group. β1-integrin is detected more frequently in colorectal cancer patients as compared with the controls (P<0.001). In colorectal cancer patients, expression of β1-integrin is significantly decreased after operation (P<0.001). β-actin is an internal control.
      Fig. 3 Correlation of β1-integrin & carcinoembryonic antigen (CEA). Expression of β1-integrin is significantly associated with that of CEA. (A) In control group, there is a moderate-positive correlation between β1-integrin and CEA (r=0.446, P=0.014). (B) In preoperative status of experimental group, there is a moderate positive correlation between β1-integrin and CEA (r=0.516, P=0.003). (C) In postoperative status of experimental group, there is a high-positive correlation between β1-integrin and CEA (r=0.935, P<0.001).
      Role of β1-Integrin in Colorectal Cancer: Case-Control Study

      Primers used for amplification

      CEA, carcinoembryonic antigen; F, forward; R, reverse.

      Characteristics

      *Statistically not significant between experimental and control group.

      Expression of CEA according to the clinicopathologic findings

      Expression of CEA in control and experimental groups

      *Expression of carcinoembryonic antigen (CEA) was detected more in experimental group rather than in control group (P=0.008).

      Density of CEA was higher in experimental group as compared with the controls (P<0.001).

      Expression of CEA was more significantly decreased after operation (P=0.032).

      §Density of CEA was significantly decreased after operation (P<0.001).

      Expression of β1-integrin according to the clinicopathologic findings

      Expression of β1-integrin in control and experimental groups

      *Expression of β1-integrin was detected more in experimental group rather than in control group (P<0.001).

      Density of β1-integrin was higher in experimental group as compared with the controls (P<0.001).

      Expression of β1-integrin was more significantly decreased after operation (P<0.001).

      §Density of β1-integrin was significantly decreased after operation (P<0.001).

      Correlation of β1-integrin & CEA

      CEA, carcinoembryonic antigen.

      Table 1 Primers used for amplification

      CEA, carcinoembryonic antigen; F, forward; R, reverse.

      Table 2 Characteristics

      *Statistically not significant between experimental and control group.

      Table 3 Expression of CEA according to the clinicopathologic findings

      Table 4 Expression of CEA in control and experimental groups

      *Expression of carcinoembryonic antigen (CEA) was detected more in experimental group rather than in control group (P=0.008).

      Density of CEA was higher in experimental group as compared with the controls (P<0.001).

      Expression of CEA was more significantly decreased after operation (P=0.032).

      §Density of CEA was significantly decreased after operation (P<0.001).

      Table 5 Expression of β1-integrin according to the clinicopathologic findings

      Table 6 Expression of β1-integrin in control and experimental groups

      *Expression of β1-integrin was detected more in experimental group rather than in control group (P<0.001).

      Density of β1-integrin was higher in experimental group as compared with the controls (P<0.001).

      Expression of β1-integrin was more significantly decreased after operation (P<0.001).

      §Density of β1-integrin was significantly decreased after operation (P<0.001).

      Table 7 Correlation of β1-integrin & CEA

      CEA, carcinoembryonic antigen.

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