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. 1995 Mar 28;92(7):2730–2734. doi: 10.1073/pnas.92.7.2730

Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas.

A Okada 1, J P Bellocq 1, N Rouyer 1, M P Chenard 1, M C Rio 1, P Chambon 1, P Basset 1
PMCID: PMC42292  PMID: 7708715

Abstract

From breast cancer cDNA libraries, we have cloned cDNAs that proved to correspond to the membrane-type matrix metalloproteinase (MT-MMP) recently identified in human placenta and proposed to be an activator of progelatinase A [Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E. & Seiki, M. (1994) Nature (London) 370, 61-65]. Using one of these cDNAs as a probe, we have detected MT-MMP gene expression in all 83 human carcinoma specimens examined by RNA in situ hybridization and have found MT-MMP transcripts in fibroblastic cells of tumor stroma but not in cancer cells. Comparison with other MMP genes expressed in fibroblastic cells of human carcinomas indicated that the expression pattern of the MT-MMP gene was more closely related to that of the gelatinase A gene than to those of the stromelysin 3 or interstitial collagenase genes. These observations are consistent with the hypothesis that MT-MMP and gelatinase A are cooperating during tumor progression and strengthen the concept that proteolytic activities originating from the stromal component of human carcinomas have a critical role in tumor progression.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Basset P., Bellocq J. P., Wolf C., Stoll I., Hutin P., Limacher J. M., Podhajcer O. L., Chenard M. P., Rio M. C., Chambon P. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 1990 Dec 20;348(6303):699–704. doi: 10.1038/348699a0. [DOI] [PubMed] [Google Scholar]
  2. Blasi F. Urokinase and urokinase receptor: a paracrine/autocrine system regulating cell migration and invasiveness. Bioessays. 1993 Feb;15(2):105–111. doi: 10.1002/bies.950150206. [DOI] [PubMed] [Google Scholar]
  3. Bosenberg M. W., Pandiella A., Massagué J. The cytoplasmic carboxy-terminal amino acid specifies cleavage of membrane TGF alpha into soluble growth factor. Cell. 1992 Dec 24;71(7):1157–1165. doi: 10.1016/s0092-8674(05)80064-9. [DOI] [PubMed] [Google Scholar]
  4. Docherty A. J., O'Connell J., Crabbe T., Angal S., Murphy G. The matrix metalloproteinases and their natural inhibitors: prospects for treating degenerative tissue diseases. Trends Biotechnol. 1992 Jun;10(6):200–207. doi: 10.1016/0167-7799(92)90214-g. [DOI] [PubMed] [Google Scholar]
  5. Dvorak H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986 Dec 25;315(26):1650–1659. doi: 10.1056/NEJM198612253152606. [DOI] [PubMed] [Google Scholar]
  6. Ehlers M. R., Riordan J. F. Membrane proteins with soluble counterparts: role of proteolysis in the release of transmembrane proteins. Biochemistry. 1991 Oct 22;30(42):10065–10074. doi: 10.1021/bi00106a001. [DOI] [PubMed] [Google Scholar]
  7. Emonard H. P., Remacle A. G., Noël A. C., Grimaud J. A., Stetler-Stevenson W. G., Foidart J. M. Tumor cell surface-associated binding site for the M(r) 72,000 type IV collagenase. Cancer Res. 1992 Oct 15;52(20):5845–5848. [PubMed] [Google Scholar]
  8. Folkman J., Shing Y. Angiogenesis. J Biol Chem. 1992 Jun 5;267(16):10931–10934. [PubMed] [Google Scholar]
  9. Freije J. M., Díez-Itza I., Balbín M., Sánchez L. M., Blasco R., Tolivia J., López-Otín C. Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem. 1994 Jun 17;269(24):16766–16773. [PubMed] [Google Scholar]
  10. Gray S. T., Yun K., Motoori T., Kuys Y. M. Interstitial collagenase gene expression in colonic neoplasia. Am J Pathol. 1993 Sep;143(3):663–671. [PMC free article] [PubMed] [Google Scholar]
  11. Höyhtyä M., Fridman R., Komarek D., Porter-Jordan K., Stetler-Stevenson W. G., Liotta L. A., Liang C. M. Immunohistochemical localization of matrix metalloproteinase 2 and its specific inhibitor TIMP-2 in neoplastic tissues with monoclonal antibodies. Int J Cancer. 1994 Feb 15;56(4):500–505. doi: 10.1002/ijc.2910560408. [DOI] [PubMed] [Google Scholar]
  12. Lefebvre O., Wolf C., Limacher J. M., Hutin P., Wendling C., LeMeur M., Basset P., Rio M. C. The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. J Cell Biol. 1992 Nov;119(4):997–1002. doi: 10.1083/jcb.119.4.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matrisian L. M. The matrix-degrading metalloproteinases. Bioessays. 1992 Jul;14(7):455–463. doi: 10.1002/bies.950140705. [DOI] [PubMed] [Google Scholar]
  14. Mignatti P., Rifkin D. B. Biology and biochemistry of proteinases in tumor invasion. Physiol Rev. 1993 Jan;73(1):161–195. doi: 10.1152/physrev.1993.73.1.161. [DOI] [PubMed] [Google Scholar]
  15. Polette M., Clavel C., Cockett M., Girod de Bentzmann S., Murphy G., Birembaut P. Detection and localization of mRNAs encoding matrix metalloproteinases and their tissue inhibitor in human breast pathology. Invasion Metastasis. 1993;13(1):31–37. [PubMed] [Google Scholar]
  16. Poulsom R., Hanby A. M., Pignatelli M., Jeffery R. E., Longcroft J. M., Rogers L., Stamp G. W. Expression of gelatinase A and TIMP-2 mRNAs in desmoplastic fibroblasts in both mammary carcinomas and basal cell carcinomas of the skin. J Clin Pathol. 1993 May;46(5):429–436. doi: 10.1136/jcp.46.5.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pyke C., Ralfkiaer E., Tryggvason K., Danø K. Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer. Am J Pathol. 1993 Feb;142(2):359–365. [PMC free article] [PubMed] [Google Scholar]
  18. Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., Seiki M. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994 Jul 7;370(6484):61–65. doi: 10.1038/370061a0. [DOI] [PubMed] [Google Scholar]
  19. Stetler-Stevenson W. G., Aznavoorian S., Liotta L. A. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol. 1993;9:541–573. doi: 10.1146/annurev.cb.09.110193.002545. [DOI] [PubMed] [Google Scholar]
  20. Wolf C., Rouyer N., Lutz Y., Adida C., Loriot M., Bellocq J. P., Chambon P., Basset P. Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1843–1847. doi: 10.1073/pnas.90.5.1843. [DOI] [PMC free article] [PubMed] [Google Scholar]

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