Multifunctional Role of Matrix Metalloproteinases in Multiple Myeloma: a Study in the 5T2MM Mouse Model

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2004 Aug 28

PMID 15331411

Citations 16

Authors

Els Van Valckenborgh

Peter I Croucher

Hendrik De Raeve

Chris Carron

Evy De Leenheer

Sylvia Blacher

Laetitia Devy

Agnes Noel

Elke de Bruyne

Kewal Asosingh

Ivan Van Riet

Ben Van Camp

Karin Vanderkerken

Affiliations

Soon will be listed here.

Abstract

Matrix metalloproteinases (MMPs) are known to play a role in cell growth, invasion, angiogenesis, metastasis, and bone degradation, all important events in the pathogenesis of cancer. Multiple myeloma is a B-cell cancer characterized by the proliferation of malignant plasma cells in the bone marrow, increased angiogenesis, and the development of osteolytic bone disease. The role of MMPs in the development of multiple myeloma is poorly understood. Using SC-964, a potent inhibitor of several MMPs (MMP-2, -3, -8, -9, and -13), we investigated the role of MMPs in the 5T2MM murine model. Reverse transcriptase-polymerase chain reaction demonstrated the presence of mRNA for MMP-2, -8, -9, and -13 in 5T2MM-diseased bone marrow. Mice bearing 5T2MM cells were given access to food containing SC-964. The concentration of SC-964 measured in the plasma of mice after 11 days of treatment was able to inhibit MMP-9 activity in gelatin zymography. Treatment of 5T2MM-bearing mice resulted in a significant reduction in tumor burden, a significant decrease in angiogenesis, and partially protective effect against the development of osteolytic bone disease. The direct role of MMPs in these different processes was confirmed by in vitro experiments. All these results support the multifunctional role of MMPs in the development of multiple myeloma.

Citing Articles

Targeted therapy for multiple myeloma: an overview on CD138-based strategies.

Riccardi F, Tangredi C, Dal Bo M, Toffoli G Front Oncol. 2024; 14:1370854.

PMID: 38655136 PMC: 11035824. DOI: 10.3389/fonc.2024.1370854.

Multiple Myeloma Derived Extracellular Vesicle Uptake by Monocyte Cells Stimulates IL-6 and MMP-9 Secretion and Promotes Cancer Cell Migration and Proliferation.

Sheridan R, Brennan K, Bazou D, OGorman P, Matallanas D, Mc Gee M Cancers (Basel). 2024; 16(5).

PMID: 38473370 PMC: 10930391. DOI: 10.3390/cancers16051011.

Possible mechanisms of action of clarithromycin and its clinical application as a repurposing drug for treating multiple myeloma.

Takemori N, Ooi H, Imai G, Hoshino K, Saio M Ecancermedicalscience. 2020; 14:1088.

PMID: 33014130 PMC: 7498274. DOI: 10.3332/ecancer.2020.1088.

Knockdown Promotes Migration and Invasion in Multiple Myeloma Cells via NF-κB Activation.

Pang M, Li C, Zheng D, Wang Y, Wang J, Zhang W Cancer Manag Res. 2020; 12:7857-7865.

PMID: 32922084 PMC: 7457837. DOI: 10.2147/CMAR.S237330.

The Role of MMP8 in Cancer: A Systematic Review.

Juurikka K, Butler G, Salo T, Nyberg P, Astrom P Int J Mol Sci. 2019; 20(18).

PMID: 31514474 PMC: 6770849. DOI: 10.3390/ijms20184506.

References

Thabard W, Barille S, Collette M, Harousseau J, Rapp M, Bataille R . Myeloma cells release soluble interleukin-6Ralpha in relation to disease progression by two distinct mechanisms: alternative splicing and proteolytic cleavage. Clin Cancer Res. 1999; 5(10):2693-7. View

Vande Broek I, Asosingh K, Allegaert V, Leleu X, Facon T, Vanderkerken K . Bone marrow endothelial cells increase the invasiveness of human multiple myeloma cells through upregulation of MMP-9: evidence for a role of hepatocyte growth factor. Leukemia. 2004; 18(5):976-82. DOI: 10.1038/sj.leu.2403331. View

Vanderkerken K, de Greef C, Asosingh K, Arteta B, De Veerman M, Vande Broek I . Selective initial in vivo homing pattern of 5T2 multiple myeloma cells in the C57BL/KalwRij mouse. Br J Cancer. 2000; 82(4):953-9. PMC: 2374415. DOI: 10.1054/bjoc.1999.1024. View

Kelly T, Borset M, Abe E, Sanderson R . Matrix metalloproteinases in multiple myeloma. Leuk Lymphoma. 2000; 37(3-4):273-81. DOI: 10.3109/10428190009089428. View

Bergers G, Brekken R, McMahon G, Vu T, Itoh T, Tamaki K . Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000; 2(10):737-44. PMC: 2852586. DOI: 10.1038/35036374. View

Mangi M, Newland A . Angiogenesis and angiogenic mediators in haematological malignancies. Br J Haematol. 2000; 111(1):43-51. DOI: 10.1046/j.1365-2141.2000.02104.x. View

Sezer O, Niemoller K, Eucker J, Jakob C, Kaufmann O, Zavrski I . Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. Ann Hematol. 2000; 79(10):574-7. DOI: 10.1007/s002770000236. View

Hajitou A, Sounni N, Devy L, Grignet-Debrus C, Lewalle J, Li H . Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis. Cancer Res. 2001; 61(8):3450-7. View

Wahlgren J, Maisi P, Sorsa T, Sutinen M, Tervahartiala T, Pirila E . Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions. J Pathol. 2001; 194(2):217-24. DOI: 10.1002/path.854. View

10.

Naglich J, Gupta E, Fargnoli J, Henderson A, Lewin A, Talbott R . Inhibition of angiogenesis and metastasis in two murine models by the matrix metalloproteinase inhibitor, BMS-275291. Cancer Res. 2001; 61(23):8480-5. View

11.

Croucher P, Shipman C, Lippitt J, Perry M, Asosingh K, Hijzen A . Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood. 2001; 98(13):3534-40. DOI: 10.1182/blood.v98.13.3534. View

12.

Nemeth J, Yousif R, Herzog M, Che M, Upadhyay J, Shekarriz B . Matrix metalloproteinase activity, bone matrix turnover, and tumor cell proliferation in prostate cancer bone metastasis. J Natl Cancer Inst. 2002; 94(1):17-25. DOI: 10.1093/jnci/94.1.17. View

13.

Bloomston M, Shafii A, Zervos E, Rosemurgy A . TIMP-1 overexpression in pancreatic cancer attenuates tumor growth, decreases implantation and metastasis, and inhibits angiogenesis. J Surg Res. 2002; 102(1):39-44. DOI: 10.1006/jsre.2001.6318. View

14.

Blacher S, Devy L, Burbridge M, Roland G, Tucker G, Noel A . Improved quantification of angiogenesis in the rat aortic ring assay. Angiogenesis. 2002; 4(2):133-42. DOI: 10.1023/a:1012251229631. View

15.

Van Valckenborgh E, De Raeve H, Devy L, Blacher S, Munaut C, Noel A . Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo. Br J Cancer. 2002; 86(5):796-802. PMC: 2375323. DOI: 10.1038/sj.bjc.6600137. View

16.

Sounni N, Devy L, Hajitou A, Frankenne F, Munaut C, Gilles C . MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression. FASEB J. 2002; 16(6):555-64. DOI: 10.1096/fj.01-0790com. View

17.

Asosingh K, Radl J, Van Riet I, Van Camp B, Vanderkerken K . The 5TMM series: a useful in vivo mouse model of human multiple myeloma. Hematol J. 2002; 1(5):351-6. DOI: 10.1038/sj.thj.6200052. View

18.

Egeblad M, Werb Z . New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002; 2(3):161-74. DOI: 10.1038/nrc745. View

19.

Xu J, Lai R, Kinoshita T, Nakashima N, Nagasaka T . Proliferation, apoptosis, and intratumoral vascularity in multiple myeloma: correlation with the clinical stage and cytological grade. J Clin Pathol. 2002; 55(7):530-4. PMC: 1769685. DOI: 10.1136/jcp.55.7.530. View

20.

O-Charoenrat P, Rhys-Evans P, Eccles S . A synthetic matrix metalloproteinase inhibitor prevents squamous carcinoma cell proliferation by interfering with epidermal growth factor receptor autocrine loops. Int J Cancer. 2002; 100(5):527-33. DOI: 10.1002/ijc.10531. View