Abstract
Co-expression of several members of the matrix metalloproteinase (MMP) family is characteristic of human malignant tumours. To investigate the role of stromelysin-2 (MMP-10) in growth and invasion of skin tumours, we studied cutaneous carcinomas with high metastatic capacity (squamous cell carcinomas, SCCs), only locally destructive tumours (basal cell carcinomas, BCCs) and pre-malignant lesions (Bowen’s disease and actinic keratosis) using in situ hybridization. Expression of MMP-10 was compared with that of stromelysin-1 (MMP-3) and of MT1-MMP, the expression of which has been shown to correlate with tumour invasiveness. MMP-10 was expressed in 13/21 SSCs and 11/19 BCCs only in epithelial laminin-5 positive cancer cells, while premalignant lesions were entirely negative. MT1-MMP mRNA was detected in 19/21 SCCs both in epithelial cancer cells and stromal fibroblasts and in 14/18 BCCs only in fibroblasts. The level of MMP-10 was upregulated in a cutaneous SCC cell line (UT-SCC-7) by transforming growth factor-α and keratinocyte growth factor, and by interferon-γ in combination with transforming growth factor-β1 and tumour necrosis factor-α both in UT-SCC-7 and HaCaT cells. Our results show that MMP-10 expression does not correlate with the invasive behaviour of tumours as assessed by their histology and MT1-MMP expression, but may be induced by the wound healing and inflammatory matrix remodelling events associated with skin tumours. © 2001 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Airola K, Johansson N, Kariniemi AL, Kähäri VM and Saarialho-Kere UK (1997) Human collagenase-3 is expressed in malignant squamous epithelium of the skin. J Invest Dermatol 109: 225–231
Ala-aho R, Johansson N, Grénman R, Fusenig NE, López-Otín C and Kähäri V-M (2000) Inhibition of collagenase-3 (MMP-13) expression in transformed human keratinocytes by interferon-γ is associated with activation of extracellular signal-regulated kinase-1,2 and STAT1. Oncogene 19: 248–257
Arany I, Fleischmann CM, Tyring SK and Fleischmann WR Jr (1997) Lack of mda-6/WAF1/CIP1-mediated inhibition of cyclin-dependent kinases in interferon-alpha resistant murine B16 melanoma cells. Cancer Lett 119: 237–240
Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, De Carlo A and Engler JA (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4: 197–250
Bord S, Horner A, Hembry RM and Compston JE (1998) Stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) expression in developing human bone: potential roles in skeletal development. Bone 23: 7–12
Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE and Gearing JA (1997) Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview. J Neuroimmunol 72: 155–161
Chomczynski P and Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159
d’Ortho MP, Will H, Atkinson S, Butler G, Messent A, Gavrilovic J, Smith B, Timpl R, Zardi L and Murphy G (1997) Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. Eur J Biochem 250: 751–757
Fort P, Marty L, Piechaczyk M, El Sabrouty S, Dani C, Jeanteur P and Blanchard JM (1985) Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res 13: 1431–1441
Giannelli G, Pozzi A, Stetler-Stevenson WG, Gardner HA and Quaranta V (1999) Expression of matrix metalloprotease-2-cleaved laminin-5 in breast remodeling stimulated by sex steroids. Am J Pathol 154: 1193–1201
Gilles C, Polette M, Piette J, Munaut C, Thompson EW, Birembaut P and Foidart JM (1996) High level of MT-MMP expression is associated with invasiveness of cervical cancer cells. Int J Cancer 65: 209–213
Harada T, Arii S, Mise M, Imamura T, Higashitsuji H, Furutani M, Niwano M, Ishigami S, Fukumoto M, Seiki M, Sato H and Imamura M (1998) Membrane-type matrix metalloproteinase-1 (MT1-MTP) gene is overexpressed in highly invasive hepatocellular carcinomas. J Hepatol 28: 231–239
Heppner KJ, Lynn MM, Jensen RA and Rodgers WH (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol 149: 273–282
Johansson N, Westermarck J, Leppä S, Häkkinen L, Koivisto L, López-Otín C, Peltonen J, Heino J and Kähäri VM (1997a) Collagenase-3 (MMP-13) gene expression by HaCaT keratinocytes is enhanced by tumor necrosis factor-α and transforming growth factor-β. Cell Growth Differ 8: 243–250
Johansson N, Airola K, Grenman R, Kariniemi AL, Saarialho-Kere U and Kähäri VM (1997b) Expression of collagenase-3 (matrix metalloproteinase-13) in squamous cell carcinomas of the head and neck. Am J Pathol 151: 499–508
Johansson N, Vaalamo M, Grénman S, Hietanen S, Klemi P, Saarialho-Kere U and Kähäri VM (1999) Collagenase-3 (MMP-13) is expressed by tumor cells in invasive vulvar squamous cell carcinomas. Am J Pathol 154: 469–480
Kadono Y, Okada Y, Namiki M, Seiki M and Sato H (1998) Transformation of epithelial Madin-Darby canine kidney cells with p60(v-src) induces expression of membrane-type 1 matrix metalloproteinase and invasiveness. Cancer Res 58: 2240–2244
Kähäri V-M and Saarialho-Kere U (1999) Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med 31: 34–45
Kainulainen T, Häkkinen L, Hamidi S, Larjava K, Kallioinen M, Peltonen J, Salo T, Larjava H and Oikarinen A (1998) Laminin-5 expression is independent of the injury and the microenvironment during reepithelialization of wounds. J Histochem Cytochem 46: 353–360
Karelina TV, Goldberg GI and Eisen AZ (1994) Matrilysin (PUMP) correlates with dermal invasion during appendageal development and cutaneous neoplasia. J Invest Dermatol 103: 482–487
Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nickoloff BJ and Uyemura K (1995) IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. J Immunol 155: 2240–2247
Knäuper V and Murphy G (1998) Membrane-type matrix metalloproteinases and cell-surface-associated activation cascades for matrix metalloproteinases. In: Matrix metalloproteinases, Parks WC, Mecham RP (eds) pp. 199–218, Academic Press: San Diego
Knäuper V, Lopez-Otin C, Smith B, Knight G and Murphy G (1996a) Biochemical characterization of human collagenase-3. J Biol Chem 271: 1544–1550
Knäuper V, Murphy G and Tschesche H (1996b) Activation of human neutrophil procollagenase by stromelysin 2. Eur J Biochem 235: 187–191
Knäuper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, Stanton H, Hembry RM and Murphy G (1996c) 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: 17124–17131
Koshikawa N, Giannelli G, Cirulli V, Miyazaki K and Quaranta V (2000) Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5. J Cell Biol 148: 615–624
Lichtinghagen R, Helmbrecht T, Arndt B and Boker KH (1995) Expression pattern of matrix metalloproteinases in human liver. Eur J Clin Chem Clin Biochem 33: 65–71
Llano E, Pendas AM, Freije JP, Nakano A, Knäuper V, Murphy G and Lopez-Otin C (1999) Identification and characterization of human MT5-MMP, a new membrane-bound activator of progelatinase a overexpressed in brain tumors. Cancer Res 59: 2570–2576
Lohi J, Lehti K, Westermarck J and Kähäri V-M and Keski-Oja J (1996) Regulation of membrane type metalloproteinase-1 expression by growth factors and phorbol 12-myristate 13-acetate. Eur J Biochem 239: 239–247
Madlener M, Mauch C, Conca W, Brauchle M, Parks WC and Werner S (1996) Regulation of the expression of stromelysin-2 by growth factors in keratinocytes: implications for normal and impaired wound healing. Biochem J 320: 659–664
Matrisian LM, McDonnell S, Miller DB, Navre M, Seftor EA and Hendrix MJ (1991) The role of the matrix metalloproteinase stromelysin in the progression of squamous cell carcinomas. Am. J Med Sci 302: 157–162
McDonnell S, Navre M, Coffey RJ Jr and Matrisian LM (1991) Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas. Mol Carcinog 4: 527–533
Mori M, Mimori K, Shiraishi T, Fujie T, Baba K, Kusumoto H, Haraguchi M, Ueo H and Akiyoshi T (1997) Analysis of MT1-MMP and MMP2 expression in human gastric cancers. Int J Cancer 74: 316–321
Muller D, Quantin B, Gesnel MC, Millon-Collard R, Abecassis J and Breathnach R (1988) The collagenase gene family in humans consists of at least four members. Biochem J 253: 187–192
Muller D, Breathnach R, Engelmann A, Millon R, Brenner G, Flesch H, Dumont P, Eber M and Abecassis J (1991) Expression of collagenase-related metalloproteinase genes in human lung or head and neck tumours. Int J Cancer 48: 550–556
Murphy G, Cockett MI, Ward RV and Docherty AJP (1991) Matrix metalloproteinase degradation of elastin, type IV collagen and proteoglycan. A quantitative comparison of the activities of 95 kDa and 72 kDa gelatinases, stromelysins-1 and -2 and punctuated metalloproteinase (PUMP). Biochem J 277: 277–279
Nagase H (1998) Stromelysins 1 and 2. In: Matrix metalloproteinases, Parks WC, Mecham RP (eds) pp. 43–84, Academic Press: San Diego
Nakamura H, Fujii Y, Ohuchi E, Yamamoto E and Okada Y (1998) Activation of the precursor of human stromelysin 2 and its interactions with other matrix metalloproteinases. Eur J Biochem 253: 67–75
Nicholson R, Murphy G and Breathnach R (1989) Human and rat malignant-tumor-associated mRNAs encode stromelysin-like metalloproteinases. Biochemistry 28: 5195–5203
Ohtani H, Motohashi H, Sato H, Seiki M and Nagura H (1996) Dual over-expression pattern of membrane-type metalloproteinase-1 in cancer and stromal cells in human gastrointestinal carcinoma revealed by in situ hybridization and immunoelectron microscopy. Int J Cancer 68: 565–570
Ohuchi E, Imai K, Fujii Y, Sato H, Seiki M and Okada Y (1997) Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J Biol Chem 272: 2446–2451
Okada A, Bellocq JP, Rouyer N, Chenard MP, Rio MC, Chambon P and Basset P (1995) Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci 92: 2730–2734
Pei D (1999) Leukolysin/MMP25/MT6-MMP: a novel matrix metalloproteinase specifically expressed in the leukocyte lineage. Cell Res 9: 291–303
Polette M, Claver C, Muller D, Abecassis J, Binninger I and Birembaut P (1991) Detection of mRNAs encoding collagenase-1 and stromelysin-2 in carcinomas of the head and neck by in situ hybridization. Invasion Metast 11: 76–83
Prosser IW, Stenmark KR, Suthar M, Crouch EC, Mecham RP and Parks WC (1989) Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonar hypertension as demonstrated by in situ hybridization. Am J Pathol 135: 1073–1088
Pulyaeva H, Bueno J, Polette M, Birembaut P, Sato H, Seiki M and Thompson EW (1997) MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin Exp Metastasis 15: 111–120
Pyke C, Salo S, Ralfkiaer E, Romer J, Dano K and Tryggvason K (1995) Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas. Cancer Res 55: 4132–4139
Saarialho-Kere UK, Chang ES, Welgus HG and Parks WC (1992) Distinct localization of collagenase and TIMP expression in wound healing associated with ulcerative pyogenic granuloma. J Clin Invest 90: 1952–1957
Saarialho-Kere UK, Kovacs SO, Pentland AP, Olerud JE, Welgus HG and Parks WC (1993) Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing. J Clin Invest 92: 2858–2866
Saarialho-Kere UK, Pentland AP, Birkedal-Hansen H, Parks WC and Welgus HG (1994) Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds. J Clin Invest 94: 79–88
Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E and Seiki M (1994) A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370: 61–65
Sirum KL and Brinckerhoff CE (1989) Cloning of the genes for human stromelysin and stromelysin 2: differential expression in rheumatoid synovial fibroblasts. Biochemistry 28: 8691–8698
Skyldberg B, Salo S, Eriksson E, Aspenblad U, Moberger B, Tryggvason K and Auer G (1999) Laminin-5 as a marker of invasiveness in cervical lesions. J Natl Cancer Inst 91: 1882–1887
Sreenath T, Matrisian LM, Stetler-Stevenson W, Gattoni-Celli S and Pozzatti RO (1992) Expression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potential. Cancer Res 52: 4942–4947
Sympson CJ, Bissell MJ and Werb Z (1995) Mammary gland tumour formation in transgenic mice overexpressing stromelysin-1. Semin Cancer Biol 6: 159–163
Tamai K, Ishikawa H, Mauviel A and Uitto J (1995) Interferon-gamma coordinately upregulates matrix metalloprotease (MMP)-1 and MMP-3, but not tissue inhibitor of metalloproteases (TIMP), expression in cultured keratinocytes. J Invest Dermatol 104: 384–390
Tsukifuji R, Tagawa K, Hatamochi A and Shinkai H (1999) Expression of matrix metalloproteinase-1, -2 and -3 in squamous cell carcinoma and actinic keratosis. Br J Cancer 80: 1087–1091
Vaalamo M, Karjalainen-Lindsberg ML, Puolakkainen P, Kere J and Saarialho-Kere U (1998) Distinct expression profiles of stromelysin-2 (MMP-10), collagenase-3 (MMP-13), macrophage metalloelastase (MMP-12), and tissue inhibitor of metalloproteinases-3 (TIMP-3) in intestinal ulcerations. Am J Pathol 152: 1005–1014
Werb Z, Vu TH, Rinkenberger JL and Coussens LM (1999) Matrix-degrading proteases and angiogenesis during development and tumor formation. APMIS 107: 11–18
Windsor LJ, Grenett H, Birkedal-Hansen B, Bodden MK, Engler JA and Birkedal-Hansen H (1993) Cell type-specific regulation of SL-1 and SL-2 genes. Induction of the SL-2 gene but not the SL-1 gene by human keratinocytes in response to cytokines and phorbolesters. Biol Chem 268: 17341–17347
Yancey KB (1995) Adhesion molecules II: Interactions of keratinocytes with epidermal basement membrane. J Invest Dermatol 104: 1008–1014
Yoshizaki T, Sato H, Maruyama Y, Murono S, Furukawa M and Park CS and Seiki M (1997) Increased expression of membrane type 1-matrix metalloproteinase in head and neck carcinoma. Cancer 79: 139–144
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Kerkelä, E., Ala-aho, R., Jeskanen, L. et al. Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers. Br J Cancer 84, 659–669 (2001). https://doi.org/10.1054/bjoc.2000.1634
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2000.1634
Keywords
This article is cited by
-
Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing
Reviews in Endocrine and Metabolic Disorders (2024)
-
New perspectives on role of tumor microenvironment in progression of cutaneous squamous cell carcinoma
Cell and Tissue Research (2016)
-
Matrix metalloproteinase-10: a novel biomarker for idiopathic pulmonary fibrosis
Respiratory Research (2015)
-
Matrix metalloproteinase-10 promotes tumor progression through regulation of angiogenic and apoptotic pathways in cervical tumors
BMC Cancer (2014)
-
The non-receptor tyrosine kinase c-Src mediates the PDGF-induced association between Furin and pro-MT1-MMP in HPAC pancreatic cells
Molecular and Cellular Biochemistry (2012)