Depletion of cell surface CD44 in nonmelanoma skin tumours is associated with increased expression of matrix metalloproteinase 7
V.-M. Kosma
Institute of Clinical Medicine/Pathology and Forensic Medicine, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland
Department of Pathology, Kuopio University Hospital, Kuopio, Finland
Search for more papers by this authorV.-M. Kosma
Institute of Clinical Medicine/Pathology and Forensic Medicine, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland
Department of Pathology, Kuopio University Hospital, Kuopio, Finland
Search for more papers by this authorConflicts of interestNone declared.
Summary
Background Expression of matrix metalloproteinase (MMP)-7 and MMP-9 is low in the normal epidermis and is induced by physiological processes such as wound healing, but also malignant transformation of epidermal cells. The activity of both MMPs has been associated with the hyaluronan (HA) receptor CD44. We previously reported that the levels of CD44 and HA differ between the two types of epidermal tumours, basal (BCC) and squamous cell carcinoma (SCC), as well as between different grades of SCC.
Objectives To investigate if the immunostaining patterns of MMP-7 and MMP-9 correlate to those of CD44 and HA in BCC and SCC.
Methods Paraffin sections from 71 BCCs, 21 in situ SCCs and 27 SCCs were immunostained for MMP-7 and -9.
Results Positive immunostaining for MMP-7 and MMP-9 was found in tumour cells of both BCC and SCC, while the staining intensity tended to be stronger in SCC. The staining intensity of MMP-7 was inversely correlated with that of CD44 in both tumour types. In well-differentiated SCC, the intensity of MMP-7 was generally weak, while CD44 staining was strong and homogeneously distributed. In poorly differentiated SCC, an increase in MMP-7 was seen, and the staining intensity of CD44 became weak and was locally absent. No correlation was seen between MMP-9 and CD44 or either of the two MMPs and HA.
Conclusions Our results show that in nonmelanoma skin tumours MMP-7 and -9 are present in the tumour cells, and suggest a link between MMP-7 activity and the depletion of cell surface CD44.
References
- 1 Nabeshima K, Inoue T, Shimao Y et al. Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int 2002; 52: 255–64.
- 2 Werb Z, Chin JR. Extracellular matrix remodeling during morphogenesis. Ann N Y Acad Sci 1998; 857: 110–18.
- 3 Kerkelä E, Saarialho-Kere U. Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. Exp Dermatol 2003; 12: 109–25.
- 4 Kuivanen TT, Jeskanen L, Kyllönen L et al. Transformation-specific matrix metalloproteinases, MMP-7 and MMP-13, are present in epithelial cells of keratoacanthomas. Mod Pathol 2006; 19: 1203–12.
- 5 Vaalamo M, Weckroth M, Puolakkainen P et al. Patterns of matrix metalloproteinase and TIMP-1 expression in chronic and normally healing human cutaneous wounds. Br J Dermatol 1996; 135: 52–9.
- 6 Simonetti O, Lucarini G, Goteri G et al. VEGF is likely a key factor in the link between inflammation and angiogenesis in psoriasis: results of an immunohistochemical study. Int J Immunopathol Pharmacol 2006; 19: 751–60.
- 7 Onoue S, Kobayashi T, Takemoto Y et al. Induction of matrix metalloproteinase-9 secretion from human keratinocytes in culture by ultraviolet B irradiation. J Dermatol Sci 2003; 33: 105–11.
- 8 Wang H, Kochevar IE. Involvement of UVB-induced reactive oxygen species in TGF-beta biosynthesis and activation in keratinocytes. Free Radic Biol Med 2005; 38: 890–7.
- 9 Skiba B, Neill B, Piva TJ. Gene expression profiles of TNF-alpha, TACE, furin, IL-1beta and matrilysin in UVA- and UVB-irradiated HaCat cells. Photodermatol Photoimmunol Photomed 2005; 21: 173–82.
- 10 Impola U, Jeskanen L, Ravanti L et al. Expression of matrix metalloproteinase (MMP)-7 and MMP-13 and loss of MMP-19 and p16 are associated with malignant progression in chronic wounds. Br J Dermatol 2005; 152: 720–6.
- 11 Monhian N, Jewett BS, Baker SR et al. Matrix metalloproteinase expression in normal skin associated with basal cell carcinoma and in distal skin from the same patients. Arch Facial Plast Surg 2005; 7: 238–43.
- 12 Yu WH, Woessner JF Jr, McNeish JD et al. CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev 2002; 16: 307–23.
- 13 Yu Q, Stamenkovic I. Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev 1999; 13: 35–48.
- 14 Yu Q, Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 2000; 14: 163–76.
- 15 Bartolazzi A, Peach R, Aruffo A et al. Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development. J Exp Med 1994; 180: 53–66.
- 16 Peterson RM, Yu Q, Stamenkovic I et al. Perturbation of hyaluronan interactions by soluble CD44 inhibits growth of murine mammary carcinoma cells in ascites. Am J Pathol 2000; 156: 2159–67.
- 17 Tuhkanen AL, Tammi M, Tammi R. CD44 substituted with heparan sulfate and endo-beta-galactosidase-sensitive oligosaccharides: a major proteoglycan in adult human epidermis. J Invest Dermatol 1997; 109: 213–18.
- 18 Kugelman LC, Ganguly S, Haggerty JG et al. The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44. J Invest Dermatol 1992; 99: 886–91.
- 19 Tammi R, Agren UM, Tuhkanen AL et al. Hyaluronan metabolism in skin. Prog Histochem Cytochem 1994; 29: 1–81.
- 20 Karvinen S, Kosma VM, Tammi MI et al. Hyaluronan, CD44 and versican in epidermal keratinocyte tumours. Br J Dermatol 2003; 148: 86–94.
- 21 Wang C, Tammi M, Guo H et al. Hyaluronan distribution in the normal epithelium of esophagus, stomach, and colon and their cancers. Am J Pathol 1996; 148: 1861–9.
- 22 Sugahara KN, Hirata T, Hayasaka H et al. Tumor cells enhance their own CD44 cleavage and motility by generating hyaluronan fragments. J Biol Chem 2006; 281: 5861–8.
- 23 Kajita M, Itoh Y, Chiba T et al. Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 2001; 153: 893–904.
- 24 Nagano O, Murakami D, Hartmann D et al. Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation. J Cell Biol 2004; 165: 893–902.
- 25 Saarialho-Kere U, Kerkelä E, Jeskanen L et al. Accumulation of matrilysin (MMP-7) and macrophage metalloelastase (MMP-12) in actinic damage. J Invest Dermatol 1999; 113: 664–72.
- 26 Karelina TV, Goldberg GI, Eisen AZ. Matrilysin (PUMP) correlates with dermal invasion during appendageal development and cutaneous neoplasia. J Invest Dermatol 1994; 103: 482–7.
- 27 McGuire JK, Li Q, Parks WC. Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am J Pathol 2003; 162: 1831–43.
- 28 Ding K, Lopez-Burks M, Sanchez-Duran JA et al. Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J Cell Biol 2005; 171: 729–38.
- 29 Tanioka Y, Yoshida T, Yagawa T et al. Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer. Br J Cancer 2003; 89: 2116–21.
- 30 Weber A, Hengge UR, Stricker I et al. Protein microarrays for the detection of biomarkers in head and neck squamous cell carcinomas. Hum Pathol 2007; 38: 228–38.
- 31 Sillanpää SM, Anttila MA, Voutilainen KA et al. Prognostic significance of matrix metalloproteinase-7 in epithelial ovarian cancer and its relation to beta-catenin expression. Int J Cancer 2006; 119: 1792–9.
- 32 Leinonen T, Pirinen R, Böhm J et al. Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer. Relation to clinicopathological factors, beta-catenin and prognosis. Lung Cancer 2006; 51: 313–21.
- 33 Wakahara K, Kobayashi H, Yagyu T et al. Bikunin down-regulates heterodimerization between CD44 and growth factor receptors and subsequently suppresses agonist-mediated signaling. J Cell Biochem 2005; 94: 995–1009.
- 34 Calikoglu E, Sorg O, Tran C et al. UVA and UVB decrease the expression of CD44 and hyaluronate in mouse epidermis, which is counteracted by topical retinoids. Photochem Photobiol 2006; 82: 1342–7.
- 35 Kosunen A, Pirinen R, Ropponen K et al. CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma. Oral Oncol 2007; 43: 51–9.
- 36 Coussens LM, Tinkle CL, Hanahan D et al. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 2000; 103: 481–90.
- 37 Ågren UM, Tammi RH, Tammi MI. Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture. Free Radic Biol Med 1997; 23: 996–1001.
- 38 Karihtala P, Soini Y, Auvinen P et al. Hyaluronan in breast cancer: correlations with nitric oxide synthases and tyrosine nitrosylation. J Histochem Cytochem 2007; 55: 1191–8.
- 39 Sander CS, Chang H, Hamm F et al. Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis. Int J Dermatol 2004; 43: 326–35.
- 40 Wu H, Lotan R, Menter D et al. Expression of E-cadherin is associated with squamous differentiation in squamous cell carcinomas. Anticancer Res 2000; 20: 1385–90.
- 41 Yamamoto H, Itoh F, Iku S et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 2001; 19: 1118–27.
- 42 Wilson CL, Heppner KJ, Labosky PA et al. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci USA 1997; 94: 1402–7.