Decreased expression of matrix metalloproteinase-2 in bone marrow micro-metastasis after FOLFOX adjuvant chemotherapy for stage III colon cancer is association with an increased progression free survival and the elimination of circulating tumour cells
Main Article Content
Abstract
Introduction: FOLFOX adjuvant chemotherapy is standard practice after curative surgery for stage III colon cancer. Even so there a significative number of patients who relapse. This study investigates the expression of metallo-proteinase (MMP-2) in bone marrow micro-metastasis and the progression free survival in these patients
Methods: Bone marrow and blood samples were taken before and after chemotherapy to detect CEA expressing cancer cells and the expression of MMP-2
Results: Patients with bone marrow micro-metastasis expressing MMP-2 after chemotherapy had a lower progression free survival rate and a shorter time to relapse.
Conclusions: The detection of MMP-2 positive micro-metastasis or CTCs may provide useful information of the prognosis of stage III colon cancer patients.
Keywords:
colon cancer, micro-metastasis, MMP-2
Article Details
How to Cite
P, Murray N; R, Villalon; D, Hartmann.
Decreased expression of matrix metalloproteinase-2 in bone marrow micro-metastasis after FOLFOX adjuvant chemotherapy for stage III colon cancer is association with an increased progression free survival and the elimination of circulating tumour cells.
Medical Research Archives, [S.l.], v. 13, n. 3, mar. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6365>. Date accessed: 06 apr. 2025.
doi: https://doi.org/10.18103/mra.v3i3.6365.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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31. Bain B. Bone marrow biopsy morbidity: review of 2003. J Clin Pathol 2005; 58: 406-408 http://doi.org/10.1136/jcp.2004.0221178
2. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet 2014: 383; 1490-1502 http://doi.org10.1016/S0140(13)61649-9
3. Salvatore I, Imperatori M, Arnold E et al. Management of patients with early-stage colon cancer: guidelines of the Italian Medical Oncology Association. ESMO open 2020 5; e001001 http:/doi.org:10.1136/esmoopen-2020-001001
4. Murray NP, Villalon R, Hartmann D, Rodriguez MP, Aedo S (2021) Improvement in immune function after FOLFOX chemotherapy for stage III colon cancer is associated with improved minimal residual disease prognostic subtype and outcome. Colorectal Dis 2021; 2021; 23: 2879-2893 http:/doi.org:/10.1111/codi.15899
5. Murray NP. (2024) The role of matrix metalloproteinase-2 in the metastatic cascade: a review. Oncologia 26 27-40. xxx
6. Lu W, Kang Y. (2019) Epithelial-mesenchymal plasticity in cancer progression and metastasis. Dev Cell 2019; 49: 361-374 http://doi.org:10.1016/j.devcel2019.04.10
7. Bhattacharya R, Panda CK, Nandi S, Mukhopahyay A. An insight into metastasis: Random or evolving paradigms? Pathol Red Pract 2018; 214: 1064-1067 http://doi.org/10.1016/j.prp.2018.06.017
8. Celia-Terrassa T, Kang Y. Metastatic niche functions and therapeutic opportunities. Nat Cell Biol 2018;20: 868-877 http://doi.org/10.1038/s41556-018-01459
9. Viehl CT, Weixler B, Guller U, Dell-Kuster S, Rosenthal R, Ramser M et al. (2017). Presence of bone marrow micro-metastasis in stage I-III colon cancer patients is associated with worse disease free and overall survival. Cancer Med 2017; 6: 918-927 http://doi.org/10.1002/cM4.1056
10. 10 Ramser M, Warchkow R, Viehl CT, Kettelhack C, Zettl A, Lobbes LA et al. The simultaneous presence of isolated tumour cells and bone marrow micrometastasis in Stage I and II colon cancer-challenging the theory of a chronological pathway of tumour cell dissemination. World J Surg 2022; 46: 680-689 http://doi.org/10.1186/s12885-016-2239-8
11. Trudel D, Fradet Y, Meyer F, Harel F, Tetu B. (2009) Significance of MMP-2 expression in prostate cancer: an immunohistocehmical study, Cancer Res 2003; 63; 8511-8515
12. Royston P, Parmar MK. The use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt. Stat Med. 2011; 30(19):2409-21. http://doi.org/10.1002/sim.1274
13. Gmeiner WH. Fluoropyridine modulation of anti-tumor immune-response prospects for improved colorectal cancer treatment. Cancer 2020; 12: 1641 http://doi.org/10.103390/cancers.1206.1641
14. Li X, Slaton WB. ((2013) Molecular mechanisms of platelet and stem cell rebound after 5-fluorouracil treatment. Exp Hematol 2013; 41: 635-645 http://doi.org/10.1016/j.exphem.2013.03.003
15. Stojanoska V, Prakash M, Mc Quade R, Fraser S. Oxaliplatin alters systemic immune response. Biomed Res Int 2019.4650695 http://doi.org/10.1155/2019/4650695
16. Wu T, Dai Y. Tumor microenvironment and therapeutic response. (2017) Cancer Lett 387; 61-68 http://doi.org/10.1016/j.canlet.2016-01-043
17. Gou HF, Zhou L, Huang J, Chen XC. Intraperitoneal oxaliplatin administration inhibits the tumour micro-environment in an abdominal implantation model of colon cancer. Mol Med Rep 2018; 18: 2335-2341 http://doi.org/10.3892/mmr.2018.9219
18. Restifo NP, Dudley ME, Rosenberg SA. Adaptive immunotherapy for cancer: Harnessing the T-cell response. Nat Rev Immunol 2012; 12: 269-281 http://doi.org/10.1038/nri3191
19. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumour lymphocytes. Science 2002; 298: 850-854 http://doi.org/10.1126/sciebnce.1076514
20. Alizadeh D, Larmonier N. Chemotherapeutic targeting of cancer-induced immunosuppressive cells. Cancer Res 2014; 74: 2663-2668 http://doi.org/10.1158/0008-5472.CAN-14-0301
21. Ruan H, Leibowitz BJ, Zhang L, Yu J. Immunogenic cell death in colon cancer prevention and therapy. Mol Carcinog 2020; 59: 783-793 http://doi.org/10.1002/mc.23183
22. Gong Y, Scott E, Lu R, Xu Y, Oh WK, Yu Q. TIMP-1 promotes accumulation of cancer associated fibroblasts and cancer progression. PlusOne 2013; 8: e77366 hhtp://doi.org/10.1371/journal.pone.0077366
23. Bockelman C, Beilmann-Lehtonen I, Kaprio T, Koskensalo S, Tervahartiala T, Mustonen H et al. Serum MMP-8 and TIMP-1 predict prognosis in colorectal cancer. BMC Cancer 2018; 18: 679 http://doi.org/10.1186/s12885-018-458x
24. Oberg A, Hoyhtya M, Tavelin R, Stenling R, Lindmark G. Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and TIMP-2) in colon cancer. Anticancer Res 2000; 20 (2B): 1085-1091
25. Rai GP, Baird SK. Tissue inhibitor of matrix metalloproteinase-3 has both anti-metastatic and anti tumourigenic properties. Clin Exp Metastasis 2020; 37: 69-76 http://doi.org/10.1007/s10585-019-10017-y
26. Teng MW, Swan JB, Koebel CM, Schrieber RD, Smyth MJ. Immune mediated dormancy: an equilibrium with cancer. J Leukoc Biol 2008; 84: 988-993 http://doi.org/10.1189/jlb.1107774
27. Rasmussen HS, Mc Cann PP. Matrix metaproteinase inhibition as a novel cancer agent: a review with special focus on batimastat and marimastat. Pharmacol Ther 1997; 75: 69-75 http://doi.org/10.1016/s0163-7258(97)00023-5
28. Bramhall S, Hallissey M, Whiting J, Tierney G, Stuart R, Hawkins R et al. Marimastat as maintenance therapy for patients with advanced gastric cancer- a randomized trial. Br J Cancer 2002; 86: 1864-1870 http://doi.org/10.1038/sj.bjc.6600816
29. Hirte H, Vergote IB, Jeffery JR, Grimshaw S, Coppieters B, Schwartz B et al. A phase III randomized trial of BAY12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: a National Cancer Institute of Canada Clinical Trials Group Study. Gynecol Oncol 2006, 102: 300-308. http://doi.org/10.1016/j.ygyno.2005.12.020
30. Bissett D, O´Bryne KJ, von Pawel J, Gatzmeier U, Price A, Nicolson M et al. (2005) Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small cell lung cancer. J Clin Oncol 2005; 23: 842-849 http://doi.org/10.1200/jco.2005.03.170
31. Bain B. Bone marrow biopsy morbidity: review of 2003. J Clin Pathol 2005; 58: 406-408 http://doi.org/10.1136/jcp.2004.0221178