Advertisement

Role of Matrix Metalloproteinases in Colorectal Cancer

  • Neha Merchant
  • Gayathri Chalikonda
  • Ganji Purnachandra NagarajuEmail author
Chapter
  • 30 Downloads
Part of the Diagnostics and Therapeutic Advances in GI Malignancies book series (DTAGIM)

Abstract

Colorectal cancer or CRC is amongst the top three leading causes of cancer related fatalities in the US. Advanced stages of CRC have very restricted treatment options. Matrix metalloproteinases (MMPs) are vital to maintain extracellular homeostasis, however, they play an important in CRC invasion and progression. Activities of MMP1, MMP2, MMP3, MMP7, MMP9, MMP13, and MT1-MMP are overexpressed in CRC and associated with worse results, whereas activities of MMP12 is known to be protective. Therefore, MMPs have become an important therapeutic target. Earlier clinical trials by broad-spectrum inhibitors of MMP have proven to be unsuccessful due to off-target toxicity as well as lack of efficiency. Currently, safe and selective inhibitors have transformed its therapeutic ability to target MMPs.

Keywords

Colorectal cancer Growth Metastasis Matrix metalloproteinases Therapy 

Abbreviations

CRC

Colorectal cancer

MMP

Matrix metalloproteinases

TIMP

Tissue Inhibitors of Metalloproteinase

mRNA

microRNA

References

  1. Adachi Y, Yamamoto H, Itoh F, Hinoda Y, Okada Y, Imai K (1999) Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers. Gut 45:252–258PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bendardaf R, Buhmeida A, Ristamäki R, Syrjänen K, Pyrhönen S (2007) MMP-1 (collagenase-1) expression in primary colorectal cancer and its metastases. Scand J Gastroenterol 42:1473–1478PubMedCrossRefPubMedCentralGoogle Scholar
  3. Bourboulia D, Stetler-Stevenson WG (2010) Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Semin Cancer Biol 20:161–168PubMedPubMedCentralCrossRefGoogle Scholar
  4. Brabletz T, Jung A, Dag S, Hlubek F, Kirchner T (1999) β-Catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol 155:1033–1038PubMedPubMedCentralCrossRefGoogle Scholar
  5. Clapper ML, Hensley HH, Chang W-CL, Devarajan K, Nguyen MT, Cooper HS (2011) Detection of colorectal adenomas using a bioactivatable probe specific for matrix metalloproteinase activity. Neoplasia 13:685–691PubMedPubMedCentralCrossRefGoogle Scholar
  6. Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer—trials and tribulations. Science 295:2387–2392PubMedCrossRefGoogle Scholar
  7. Decock J, Paridaens R, Ye S (2008) Genetic polymorphisms of matrix metalloproteinases in lung, breast and colorectal cancer. Clin Genet 73:197–211PubMedCrossRefPubMedCentralGoogle Scholar
  8. Decock J, Thirkettle S, Wagstaff L, Edwards DR (2011) Matrix metalloproteinases: protective roles in cancer. J Cell Mol Med 15:1254–1265PubMedPubMedCentralCrossRefGoogle Scholar
  9. Dragutinović VV, Radonjić NV, Petronijević ND, Tatić SB, Dimitrijević IB, Radovanović NS, Krivokapić ZV (2011) Matrix metalloproteinase-2 (MMP-2) and-9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer. Mol Cell Biochem 355:173–178PubMedCrossRefGoogle Scholar
  10. Garg P, Sarma D, Jeppsson S, Patel NR, Gewirtz AT, Merlin D, Sitaraman SV (2010) Matrix metalloproteinase-9 functions as a tumor suppressor in colitis-associated cancer. Cancer Res 70:792–801PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hasegawa S, Koshikawa N, Momiyama N, Moriyama K, Ichikawa Y, Ishikawa T, Mitsuhashi M, Shimada H, Miyazaki K (1998) Matrilysin-specific antisense oligonucleotide inhibits liver metastasis of human colon cancer cells in a nude mouse model. Int J Cancer 76:812–816PubMedCrossRefGoogle Scholar
  12. Hilska M, Roberts PJ, Collan YU, Laine VJO, Kössi J, Hirsimäki P, Rahkonen O, Laato M (2007) Prognostic significance of matrix metalloproteinases-1,-2,-7 and-13 and tissue inhibitors of metalloproteinases-1,-2,-3 and-4 in colorectal cancer. Int J Cancer 121:714–723PubMedCrossRefGoogle Scholar
  13. Holten-Andersen MN, Christensen IJ, Nielsen HJ, Stephens RW, Jensen V, Nielsen OH, Sørensen S, Overgaard J, Lilja H, Harris A (2002) Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer. Clin Cancer Res 8:156–164PubMedGoogle Scholar
  14. Hu J, Van den Steen PE, Sang Q-XA, Opdenakker G (2007) Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 6:480PubMedCrossRefGoogle Scholar
  15. Hua H, Li M, Luo T, Yin Y, Jiang Y (2011) Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci 68:3853–3868PubMedCrossRefGoogle Scholar
  16. Huang M-Y, Chang H-J, Chung F-Y, Yang M-J, Yang Y-H, Wang J-Y, Lin S-R (2010) MMP13 is a potential prognostic marker for colorectal cancer. Oncol Rep 24:1241–1247PubMedCrossRefGoogle Scholar
  17. Ii M, Yamamoto H, Adachi Y, Maruyama Y, Shinomura Y (2006) Role of matrix metalloproteinase-7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis. Exp Biol Med 231:20–27CrossRefGoogle Scholar
  18. Inuzuka K, Ogata Y, Nagase H, Shirouzu K (2000) Significance of coexpression of urokinase-type plasminogen activator, and matrix metalloproteinase 3 (stromelysin) and 9 (gelatinase B) in colorectal carcinoma. J Surg Res 93:211–218PubMedCrossRefGoogle Scholar
  19. Kim Y-S, Ahn YH, Song KJ, Kang JG, Lee JH, Jeon SK, Kim H-C, Yoo JS, Ko J-H (2012) Overexpression and β-1, 6-N-Acetylglucosaminylation-initiated aberrant glycosylation of TIMP-1 A “DOUBLE WHAMMY” STRATEGY IN COLON CANCER PROGRESSION. J Biol Chem 287:32467–32478PubMedPubMedCentralCrossRefGoogle Scholar
  20. Knäuper V, Will H, López-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM, Murphy G (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271:17124–17131PubMedCrossRefPubMedCentralGoogle Scholar
  21. Kryczka J, Stasiak M, Dziki L, Mik M, Dziki A, Cierniewski CS (2012) Matrix metalloproteinase-2 cleavage of the β1 integrin ectodomain facilitates colon cancer cell motility. J Biol Chem 287:36556–36566PubMedPubMedCentralCrossRefGoogle Scholar
  22. Langenskiöld M, Holmdahl L, Falk P, Ivarsson M-L (2005) Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer. Int J Color Dis 20:245–252CrossRefGoogle Scholar
  23. Lee J-H, Choi J-W, Kim Y-S (2011) Plasma or serum TIMP-1 is a predictor of survival outcomes in colorectal cancer: a meta-analysis. J Gastrointestin Liver Dis 20:287–291PubMedPubMedCentralGoogle Scholar
  24. Leeman M, McKay J, Murray GI (2002) Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer. J Clin Pathol 55:758–762PubMedPubMedCentralCrossRefGoogle Scholar
  25. Lin H, Zhang Y, Wang H, Xu D, Meng X, Shao Y, Lin C, Ye Y, Qian H, Wang S (2012) Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells. Cancer Gene Ther 19:845PubMedCrossRefPubMedCentralGoogle Scholar
  26. Loesch M, Zhi H-Y, Hou S-W, Qi X-M, Li R-S, Basir Z, Iftner T, Cuenda A, Chen G (2010) p38γ MAPK cooperates with c-Jun in trans-activating matrix metalloproteinase 9. J Biol Chem 285:15149–15158PubMedPubMedCentralCrossRefGoogle Scholar
  27. Lu KV, Jong KA, Rajasekaran AK, Cloughesy TF, Mischel PS (2004) Upregulation of tissue inhibitor of metalloproteinases (TIMP)-2 promotes matrix metalloproteinase (MMP)-2 activation and cell invasion in a human glioblastoma cell line. Lab Investig 84:8PubMedCrossRefPubMedCentralGoogle Scholar
  28. Malhotra S, Newman E, Eisenberg D, Scholes J, Wieczorek R, Mignatti P, Shamamian P (2002) Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer. Dis Colon Rectum 45:537–543PubMedCrossRefGoogle Scholar
  29. Maurel J, Nadal C, Garcia-Albeniz X, Gallego R, Carcereny E, Almendro V, Mármol M, Gallardo E, Maria Augé J, Longarón R (2007) Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients. Int J Cancer 121:1066–1071PubMedCrossRefPubMedCentralGoogle Scholar
  30. Miyazaki K, Koshikawa N, Hasegawa S, Momiyama N, Nagashima Y, Moriyama K, Ichikawa Y, Ishikawa T, Mitsuhashi M, Shimada H (1999) Matrilysin as a target for chemotherapy for colon cancer: use of antisense oligonucleotides as antimetastatic agents. Cancer Chemother Pharmacol 43:S52–S55PubMedCrossRefGoogle Scholar
  31. Ogata Y, Matono K, Nakajima M, Sasatomi T, Mizobe T, Nagase H, Shirouzu K (2006) Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat. Int J Cancer 118:215–221PubMedCrossRefGoogle Scholar
  32. Overall CM, Kleifeld O (2006) Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer 6:227PubMedCrossRefGoogle Scholar
  33. Papageorgis P, Cheng K, Ozturk S, Gong Y, Lambert AW, Abdolmaleky HM, Zhou J-R, Thiagalingam S (2011) Smad4 inactivation promotes malignancy and drug resistance of colon cancer. Cancer Res 71:998–1008PubMedPubMedCentralCrossRefGoogle Scholar
  34. Park KS, Kim SJ, Kim KH, Kim JC (2011) Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer. J Gastroenterol Hepatol 26:391–397PubMedCrossRefGoogle Scholar
  35. Powe D, Brough J, Carter G, Bailey E, Stetler-Stevenson W, Turner D, Hewitt R (1997) TIMP-3 mRNA expression is regionally increased in moderately and poorly differentiated colorectal adenocarcinoma. Br J Cancer 75:1678PubMedPubMedCentralCrossRefGoogle Scholar
  36. Roy R, Yang J, Moses MA (2009) Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 27:5287PubMedPubMedCentralCrossRefGoogle Scholar
  37. Sardinha TC, Nogueras JJ, Xiong H, Weiss EG, Wexner SD, Abramson S (2000) Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer. Dis Colon Rectum 43:389–395PubMedCrossRefPubMedCentralGoogle Scholar
  38. Shi H, Xu JM, Hu NZ, Wang XL, Mei Q, Song YL (2006) Transfection of mouse macrophage metalloelastase gene into murine CT-26 colon cancer cells suppresses orthotopic tumor growth, angiogenesis and vascular endothelial growth factor expression. Cancer Lett 233:139–150PubMedCrossRefPubMedCentralGoogle Scholar
  39. Shiozawa J, Ito M, Nakayama T, Nakashima M, Kohno S, Sekine I (2000) Expression of matrix metalloproteinase-1 in human colorectal carcinoma. Mod Pathol 13:925PubMedCrossRefPubMedCentralGoogle Scholar
  40. Sunami E, Tsuno N, Osada T, Saito S, Kitayama J, Tomozawa S, Tsuruo T, Shibata Y, Muto T, Nagawa H (2000) MMP-1 is a prognostic marker for hematogenous metastasis of colorectal cancer. Oncologist 5:108–114PubMedCrossRefGoogle Scholar
  41. Takahashi M, Nakamura Y, Obama K, Furukawa Y (2005) Identification of SP5 as a downstream gene of the β-catenin/Tcf pathway and its enhanced expression in human colon cancer. Int J Oncol 27:1483–1487PubMedPubMedCentralGoogle Scholar
  42. Van Der Jagt MF, Wobbes T, Strobbe LJ, Sweep FC, Span PN (2010) Metalloproteinases and their regulators in colorectal cancer. J Surg Oncol 101:259–269PubMedGoogle Scholar
  43. Wilson CL, Heppner KJ, Labosky PA, Hogan BL, Matrisian LM (1997) Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci 94:1402–1407PubMedCrossRefPubMedCentralGoogle Scholar
  44. Wu J, Wu G, Lv L, Ren Y-F, Zhang X-J, Xue Y-F, Li G, Lu X, Sun Z, Tang K-F (2011) MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1. Carcinogenesis 33:519–528PubMedCrossRefGoogle Scholar
  45. Xie G, Cheng K, Shant J, Raufman J-P (2009) Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells. Am J Physiol Gastrointest Liver Physiol 296:G755–G763PubMedPubMedCentralCrossRefGoogle Scholar
  46. Xu Z, Shi H, Li Q, Mei Q, Bao J, Shen Y, Xu J (2008) Mouse macrophage metalloelastase generates angiostatin from plasminogen and suppresses tumor angiogenesis in murine colon cancer. Oncol Rep 20:81–88PubMedGoogle Scholar
  47. Yang W, Arii S, Gorrin-Rivas MJ, Mori A, Onodera H, Imamura M (2001) Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance. Cancer 91:1277–1283PubMedCrossRefPubMedCentralGoogle Scholar
  48. Zhang B, Halder SK, Kashikar ND, Cho YJ, Datta A, Gorden DL, Datta PK (2010) Antimetastatic role of Smad4 signaling in colorectal cancer. Gastroenterology 138:969–980. e963PubMedCrossRefGoogle Scholar
  49. Zhang M, Liu Y, Feng H, Bian X, Zhao W, Yang Z, Gu B, Li Z, Liu Y (2013) CD133 affects the invasive ability of HCT116 cells by regulating TIMP-2. Am J Pathol 182:565–576PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Neha Merchant
    • 1
  • Gayathri Chalikonda
    • 1
  • Ganji Purnachandra Nagaraju
    • 1
    Email author
  1. 1.Department of Hematology and Medical Oncology, Winship Cancer InstituteEmory UniversityAtlantaUSA

Personalised recommendations