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Can Fibulin-5 Induce Gastrointestinal Stromal Tumor Development?

Year 2020, Volume: 3 Issue: 3, 275 - 285, 31.12.2020

Abstract

Objective:
Gastrointestinal stromal tumors are the most common primary mesenchymal tumors of the gastrointestinal tract and show Cajal cell differentiation. Fibulin-5 is a multifunctional extracellular matrix protein that inhibits epithelial and endothelial cell proliferation. Expression of fibulin-5 is down-regulated in various carcinomas. In contrast, fibulin-5 stimulates fibroblast and fibrosarcoma cells. In this study we aimed to investigate the expression of fibulin-5 in Cajal cells and gastrointestinal stromal tumors.
Materials and Methods:
Immunohistochemical fibulin-5 staining is performed on 34 (22 gastric and 12 small intestinal) gastrointestinal stromal tumors. Fibulin-5 staining intensity was scored in 4 quantitative categories and compared with clinicopathological features of the patients.
Results:
There was no staining in 4 of the gastrointestinal stromal tumors; weak staining in 20 cases, moderate staining in 6 cases, and strong staining in 4 cases were observed. In 3 cases Cajal cells were detected with fibulin-5 by moderately staining. The relationship between fibulin-5 staining intensity and age and gender of the cases, localization, size, grade, and the risk groups of the tumors wasn’t statistically significant.
Conclusion:
A great proportion of gastrointestinal stromal tumors show fibulin-5 expression, even if weak, in contrast to the infrequent fibulin-5 expression in Cajal cells. Based on these findings, it can be speculated that the expression of fibulin-5 in Cajal cells can be increase cell proliferation, but it would be useful to conduct new studies with larger series to clarify this issue. There is no correlation between fibulin-5 expression intensity and clinicopathological and prognostic data of gastrointestinal stromal tumors.

References

  • 1-Fukayama M, Goldblum JR, Miettinen M, et al. Mesenchymal tumours of the digestive system. In WHO Classification of Tumours Editorial Board, editors. Digestive system Tumours. 5th ed:439-444. Lyon, IARC Press, 2019.
  • 2-Sanders KM, Koh SD, Ward SM. Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu Rev Physiol. 2006;68:307-343. PMID: 16460275 DOI: 10.1146/annurev.physiol.68.040504.094718
  • 3-Ördög T, Redelman D, Horváth VJ, et al. Quantitative analysis by flowcytometry of interstitial cells of Cajal, pacemakers, and mediators of neurotransmission in the gastrointestinal tract. Cytometry Part A: The Journal of the International Society for Analytical Cytology. 2004;62(2):139-149. PMID: 15536638 DOI: 10.1002/cyto.a.20078
  • 4- Sanders KM, Ward SM. Kit mutants and gastrointestinal physiology. The Journal of physiology. 2007;578(1):33-42. PMID: 17095561 DOI: 10.1113/jphysiol.2006.122473
  • 5- Mostafa RM, Moustafa YM, Hamdy H. Interstitial cells of Cajal, the Maestro in health and disease. World journal of gastroenterology: WJG. 2010;16(26):3239. PMID: 20614479 DOI: 10.3748/wjg.v16.i26.3239
  • 6- Bülbül GD. Gastrointestinal stromal tumors: A multicenter study of 1160 Turkish cases. The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology. 2012;23(3):203-211. PMID: 22798108
  • 7- Albig AR, Schiemann WP. Fibulin-5 function during tumorigenesis. Future Oncol. 2005 Feb;1(1):23-35. PMID: 16555973 DOI: 10.1517/14796694.1.1.23
  • 8- Mohamedi Y, Fontanil T, Solares L, et al. Fibulin-5 downregulates Ki-67 and inhibits proliferation and invasion of breast cancer cells. Int J Oncol. 2016 Apr;48(4):1447-56. PMID: 26891749 doi: 10.3892/ijo.2016.3394.
  • 9- Lee YH, Albig AR, Regner M, et al. Fibulin-5 initiates epithelial-mesenchymal transition (EMT) and enhances EMT induced by TGF-beta in mammary epithelial cells via a MMP dependent mechanism. Carcinogenesis. 2008;29:2243–2251. PMID: 18713838 doi: 10.1093/carcin/bgn199
  • 10- Guadall A, Orriols M, Rodríguez-Calvo R, et al. Fibulin-5 is up-regulated by hypoxia in endothelial cells through a hypoxia-inducible factor-1 (HIF-1alpha)-dependent mechanism. J BiolChem. 2011; 286:7093–7103. PMID:21193390 doi: 10.1074/jbc.M110.162917
  • 10- Schiemann WP, Blobe GC, Kalume DE, et al. Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades. J BiolChem. 2002 Jul 26;277(30):27367-77. PMID: 12021267 DOI: 10.1074/jbc.M200148200
  • 11- Yanagisawa H, Schluterman MK, Brekken RA. Fibulin-5, an integrin-binding matricellular protein: its function in development and disease. Journal of cell communication and signaling. 2009;3(3-4), 337-347.
  • 12- Albig AR, Schiemann WP. Fibulin-5 antagonizes vascular endothelial growth factor (VEGF) signaling and angiogenic sprouting by endothelial cells. DNA and cell biology. 2004; 23(6): 367-379. PMID: 15231070 DOI: 10.1089/104454904323145254
  • 13- Argraves WS, Greene LM, Cooley MA, et al. Fibulins: physiological and disease perspectives. EMBO Rep. 2003 Dec;4(12):1127-31. PMID: 14647206 DOI: 10.1038/sj.embor.7400033
  • 14- Yue W, Sun Q, Landreneau R, et al. Fibulin-5 suppresses lung cancer invasion by inhibiting matrix metalloproteinase-7 expression. Cancer research. 2009; 69(15): 6339-6346. PMID: 19584278 DOI: 10.1158/0008-5472.CAN-09-0398
  • 15- Li H, Ren G, Cai R, et al. A correlation research of Ki67 index, CT features, and risk stratification in gastrointestinal stromal tumor. Cancer medicine. 2018;7(9), 4467-4474.
  • 16- Zhou Y, Hu W, Chen P, et al. Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors: a systematic review and meta-analysis. Medicine. 2017;96(34).
  • 17- Cerski MR, Pereira F, Matte US, et al. Exon 11 mutations, Ki67, and p16INK4A as predictors of prognosis in patients with GIST. Pathology-Research and Practice. 2011;207(11), 701-706.
  • 18- Basilio-de-Oliveira RP, Pannain VLN. Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors. World Journal of Gastroenterology: WJG. 2015;21(22), 6924.
  • 19- Jiang L, Cao M, Hu J, et al. Expression of PIN1 in Gastrointestinal Stromal Tumours and its Clinical Significance. Anticancer research. 2016;36(3), 1275-1280.
  • 20- Zhu K, Li K, Yuan DW, et al. Clinicopathological and Prognostic Significance of Expression of B-Cell-Specific Moloney Murine Leukemia Virus Insertion Site 1 (BMI-1) Gene and Protein in Gastrointestinal Stromal Tumors. Medical science monitor: international medical journal of experimental and clinical research. 2018;24, 6414.
  • 21- Lu J, Chen S, Li X, et al. Gastrointestinal stromal tumors: Fibrinogen levels are associated with prognosis of patients as blood-based biomarker. Medicine. 2018;97(17).
  • 22- Liu Q, Li Y, Dong M, et al. Gastrointestinal bleeding is an independent risk factor for poor prognosis in GIST patients. BioMed research international. 2017;2017.
  • 23- Yi M, Xia L, Zhou Y, et al. Prognostic value of tumor necrosis in gastrointestinal stromal tumor: A meta-analysis. Medicine. 2019;98(17).
  • 24- Haller F, Cortis J, Helfrich J, et al. Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival. Modern Pathology. 2011;24(2), 248-255.
Year 2020, Volume: 3 Issue: 3, 275 - 285, 31.12.2020

Abstract

References

  • 1-Fukayama M, Goldblum JR, Miettinen M, et al. Mesenchymal tumours of the digestive system. In WHO Classification of Tumours Editorial Board, editors. Digestive system Tumours. 5th ed:439-444. Lyon, IARC Press, 2019.
  • 2-Sanders KM, Koh SD, Ward SM. Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu Rev Physiol. 2006;68:307-343. PMID: 16460275 DOI: 10.1146/annurev.physiol.68.040504.094718
  • 3-Ördög T, Redelman D, Horváth VJ, et al. Quantitative analysis by flowcytometry of interstitial cells of Cajal, pacemakers, and mediators of neurotransmission in the gastrointestinal tract. Cytometry Part A: The Journal of the International Society for Analytical Cytology. 2004;62(2):139-149. PMID: 15536638 DOI: 10.1002/cyto.a.20078
  • 4- Sanders KM, Ward SM. Kit mutants and gastrointestinal physiology. The Journal of physiology. 2007;578(1):33-42. PMID: 17095561 DOI: 10.1113/jphysiol.2006.122473
  • 5- Mostafa RM, Moustafa YM, Hamdy H. Interstitial cells of Cajal, the Maestro in health and disease. World journal of gastroenterology: WJG. 2010;16(26):3239. PMID: 20614479 DOI: 10.3748/wjg.v16.i26.3239
  • 6- Bülbül GD. Gastrointestinal stromal tumors: A multicenter study of 1160 Turkish cases. The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology. 2012;23(3):203-211. PMID: 22798108
  • 7- Albig AR, Schiemann WP. Fibulin-5 function during tumorigenesis. Future Oncol. 2005 Feb;1(1):23-35. PMID: 16555973 DOI: 10.1517/14796694.1.1.23
  • 8- Mohamedi Y, Fontanil T, Solares L, et al. Fibulin-5 downregulates Ki-67 and inhibits proliferation and invasion of breast cancer cells. Int J Oncol. 2016 Apr;48(4):1447-56. PMID: 26891749 doi: 10.3892/ijo.2016.3394.
  • 9- Lee YH, Albig AR, Regner M, et al. Fibulin-5 initiates epithelial-mesenchymal transition (EMT) and enhances EMT induced by TGF-beta in mammary epithelial cells via a MMP dependent mechanism. Carcinogenesis. 2008;29:2243–2251. PMID: 18713838 doi: 10.1093/carcin/bgn199
  • 10- Guadall A, Orriols M, Rodríguez-Calvo R, et al. Fibulin-5 is up-regulated by hypoxia in endothelial cells through a hypoxia-inducible factor-1 (HIF-1alpha)-dependent mechanism. J BiolChem. 2011; 286:7093–7103. PMID:21193390 doi: 10.1074/jbc.M110.162917
  • 10- Schiemann WP, Blobe GC, Kalume DE, et al. Context-specific effects of fibulin-5 (DANCE/EVEC) on cell proliferation, motility, and invasion. Fibulin-5 is induced by transforming growth factor-beta and affects protein kinase cascades. J BiolChem. 2002 Jul 26;277(30):27367-77. PMID: 12021267 DOI: 10.1074/jbc.M200148200
  • 11- Yanagisawa H, Schluterman MK, Brekken RA. Fibulin-5, an integrin-binding matricellular protein: its function in development and disease. Journal of cell communication and signaling. 2009;3(3-4), 337-347.
  • 12- Albig AR, Schiemann WP. Fibulin-5 antagonizes vascular endothelial growth factor (VEGF) signaling and angiogenic sprouting by endothelial cells. DNA and cell biology. 2004; 23(6): 367-379. PMID: 15231070 DOI: 10.1089/104454904323145254
  • 13- Argraves WS, Greene LM, Cooley MA, et al. Fibulins: physiological and disease perspectives. EMBO Rep. 2003 Dec;4(12):1127-31. PMID: 14647206 DOI: 10.1038/sj.embor.7400033
  • 14- Yue W, Sun Q, Landreneau R, et al. Fibulin-5 suppresses lung cancer invasion by inhibiting matrix metalloproteinase-7 expression. Cancer research. 2009; 69(15): 6339-6346. PMID: 19584278 DOI: 10.1158/0008-5472.CAN-09-0398
  • 15- Li H, Ren G, Cai R, et al. A correlation research of Ki67 index, CT features, and risk stratification in gastrointestinal stromal tumor. Cancer medicine. 2018;7(9), 4467-4474.
  • 16- Zhou Y, Hu W, Chen P, et al. Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors: a systematic review and meta-analysis. Medicine. 2017;96(34).
  • 17- Cerski MR, Pereira F, Matte US, et al. Exon 11 mutations, Ki67, and p16INK4A as predictors of prognosis in patients with GIST. Pathology-Research and Practice. 2011;207(11), 701-706.
  • 18- Basilio-de-Oliveira RP, Pannain VLN. Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors. World Journal of Gastroenterology: WJG. 2015;21(22), 6924.
  • 19- Jiang L, Cao M, Hu J, et al. Expression of PIN1 in Gastrointestinal Stromal Tumours and its Clinical Significance. Anticancer research. 2016;36(3), 1275-1280.
  • 20- Zhu K, Li K, Yuan DW, et al. Clinicopathological and Prognostic Significance of Expression of B-Cell-Specific Moloney Murine Leukemia Virus Insertion Site 1 (BMI-1) Gene and Protein in Gastrointestinal Stromal Tumors. Medical science monitor: international medical journal of experimental and clinical research. 2018;24, 6414.
  • 21- Lu J, Chen S, Li X, et al. Gastrointestinal stromal tumors: Fibrinogen levels are associated with prognosis of patients as blood-based biomarker. Medicine. 2018;97(17).
  • 22- Liu Q, Li Y, Dong M, et al. Gastrointestinal bleeding is an independent risk factor for poor prognosis in GIST patients. BioMed research international. 2017;2017.
  • 23- Yi M, Xia L, Zhou Y, et al. Prognostic value of tumor necrosis in gastrointestinal stromal tumor: A meta-analysis. Medicine. 2019;98(17).
  • 24- Haller F, Cortis J, Helfrich J, et al. Epithelioid/mixed phenotype in gastrointestinal stromal tumors with KIT mutation from the stomach is associated with accelerated passage of late phases of the cell cycle and shorter disease-free survival. Modern Pathology. 2011;24(2), 248-255.
There are 25 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Articles
Authors

Meryem İlkay Eren Karanis 0000-0002-1097-4592

Hande Köksal 0000-0002-9668-7913

Publication Date December 31, 2020
Acceptance Date December 14, 2020
Published in Issue Year 2020 Volume: 3 Issue: 3

Cite

APA Eren Karanis, M. İ., & Köksal, H. (2020). Can Fibulin-5 Induce Gastrointestinal Stromal Tumor Development?. Journal of Cukurova Anesthesia and Surgical Sciences, 3(3), 275-285.

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