Abstract
The gene expression of matrix metalloproteinase-1 and -3 was examined in basal cell carcinomas by in situ hybridization using digoxigenin-labelled riboprobes. Nodulo-ulcerative basal cell carcinomas demonstrated the gene expression for both metalloproteinases but superficial basal cell carcinomas did not present any transcripts for them. Transcripts for matrix metalloproteinase-1 (interstitial collagenase) were demonstrated densely in stromal cells among tumour masses, and those for matrix metalloproteinase-3 (stromelysin-1) were detected only in more advanced cases. Neither were expressed in tumour cells. The two metalloproteinases were produced by stromal cells according to the tumour invasion process, in which various growth factors, cytokines and inflammatory factors, which could regulate gene expressions of matrix metalloproteinases, were involved. It was also found that hybridization signals were enhanced by treatment with chondroitin ABC lyase, which digested abundant glycosaminoglycans in basal cell carcinoma. The procedure for the digestion is simple, and appears to be of value for in situ hybridization studies on tissues containing large amounts of glycosaminoglycans.
Similar content being viewed by others
References
Angel, P., Imagawa, M., Chiu, R., Stein, B., Imbra, R.J., Rahmsdorf, H.J., Jonat, C., Herrlich, P. & Karin, M. (1987) Phorbol ester-inducible genes contain a common cis element recognized by TPA-modulated trans-acting factor. Cell 49, 729-39.
Bauer, E.A., Uitto, J., Walters, R.C. & Eisen, A.Z. (1979) Enhanced collagenase production by fibroblasts derived from human basal cell carcinomas. Cancer Res. 39, 4594-9.
Bland, Y.S., Critchlow, M.A. & Ashhurst, D.E. (1991) Digoxigenin as a probe label for in situ hybridization on skeletal tissues. Histochem. J. 23, 415-18.
Goldberg, G.I., Wilhelm, S.M., Kronberger, A., Bauer, E.A., Grant, G.A. & Eisen, A.Z. (1986) Human fibroblast collagenase. J. Biol. Chem. 261, 6600-5.
Goslen, J.B. & Bauer, E.A. (1986) Basal cell carcinoma and collagenase. J. Dermatol. Surg. Oncol. 12, 812-17.
Goslen, J.B., Eisen, A.Z. & Bauer, E.A. (1985) Stimulation of skin fibroblast collagenase production by a cytokine derived from basal cell carcinomas. J. Invest. Dermatol. 85, 161-4.
Hernandez, A.D., Hibbs, M.S. & Postlethwaite, A.E. (1985) Establishment of basal cell carcinoma in culture: evidence for a basal cell carcinoma derived factor(s) which stimulates fibroblasts to proliferate and release collagenase. J. Invest. Dermatol. 85, 470-5.
Ino, H., Ishizuka, T., Chiba, T. & Tatibana, M. (1994) Expression of CDK5 (PSSALRE kinase), a neural cdc2-related protein kinase, in the mature and developing mouse central and peripheral nervous systems. Brain Res. 661, 196-206.
Inoue, M., Kratz, G., Haegerstrand, A. & StÅhle-BÄckdahl, M. (1995) Collagenase expression is rapidly induced in wound-edge keratinocytes after acute injury in human skin, persists during healing, and stops at re-epithelialization. J. Invest. Dermatol. 104, 479-83.
Lever, W.F. & Schaumburg-Lever, G. (1989) Basal cell epithelioma. In Tumors of the Epidermal Appendages. Histopathology of the Skin, 7th edn (edited by Lever, W. F. & Schaumburg-Lever, G.), pp. 622-634. Philadelphia: J. B. Lippincott.
Majmudar, G., Nelson, B.R., Jensen, T.C. & Johnson, T. M. (1994) Increased expression of matrix metalloproteinase-3 (stromelysin-1) in cultured fibroblasts and basal cell carcinomas of nevoid basal cell carcinoma syndrome. Mol. Carcinogen. 11, 29-33.
Mauviel, A. (1993) Cytokine regulation of metalloproteinase gene expression. J. Cell. Biochem. 53, 288-95.
Mauviel, A., Halcin, C., Vasiloudes, P., Parks, W.C. & Kurkinen, M. (1994) Uncoordinate regulation of collagenase, stromelysin, and tissue inhibitor of metalloproteinases genes by prostaglandin E2: selective enhancement of collagenase gene expression in human dermal fibroblasts in culture. J. Cell. Biochem. 54, 465-72.
Muller, D., Wolf, C., Abecassis, J., Millon, R., Engelmann, A., Bronner, G., Rouyer, N., Rio, M.-C., Eber, M., Methlin, G., Chambon, P. & Basset, P. (1993) Increased stromelysin 3 gene expression is associated with increased local invasiveness in head and neck squamous cell carcinomas. Cancer Res. 53, 165-9.
Otani, Y., Quinones, S., Saus, J., Kurkinen, M. & Harris, E. D. jr (1990) Cycloheximide induces stromelysin mRNA in cultured human fibroblasts. Eur. J. Biochem. 192, 75-9.
Poulsom, R., Hanby, A.M., Pignatelli, M., Jeffery, R.E., Longcroft, J.M., Rogers, L. & Stamp, G.W.H. (1993) 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. 46, 429-36.
Pyke, C., RalfkiÆr, E., Huhtala, P., Hurskainen, T., DanØ, K. & Tryggvason, K. (1992) Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers by in situ hybridization. Cancer Res. 52, 1336-41.
Saus, J., Quinones, S., Otani, Y., Nagase, H., Harris, E. D. & Kurkinen, M. (1988) The complete primary structure of human matrix metalloproteinase-3. J. Biol. Chem. 263, 6742-5.
Shinkai, H. (1993) Proteoglycans: structure, biosynthesis, and degradation. In Connective Tissue Diseases of the Skin (edited by LapiÉre C. M. & Krieg, T.). pp. 17-30. Basel: Marcel Dekker.
Spiers, E.M., Lazarus, G.S. & Lyons-Giordano, B. (1996) Expression of plasminogen activators in basal cell carcinoma. J. Pathol. 178, 290-6.
Suzuki, K., Enghild, J.J., Morodomi, T., Salvesen, G. & Nagase, H. (1990) Mechanisms of activation of tissue procollagenase by matrix metalloproteinase 3 (stromelysin). Biochemistry 29, 10261-70.
UndÉn, A.B., Sandstedt, B., Bruce, K., Hedblad, M.-A. & StÅhle-BÄckdahl, M. (1996) Stromelysin-3 mRNA associated with myofibroblasts is overexpressed in aggressive basal cell carcinoma and in dermatofibroma but not in dermatofibrosarcoma. J. Invest. Dermatol. 107, 147-53.
Vaalamo, M., Weckroth, M., Puolakkainen, P., Kere, J., Saarinen, P., Lauharanta, J. & Saarialho-Kere, U. K. (1996) Patterns of matrix metalloproteinase and TIMP-1 expression in chronic and normally healing human cutaneous wounds. Br. J. Dermatol. 135, 52-9.
Wolf, C., Chenard M.-P., De Grossouvre, P.D., Bellocq, J.-P., Chambon, P. & Basset, P. (1992) Breast cancer-associated stromelysin-3 gene is expressed in basal cell carcinoma and during cutaneous wound healing. J. Invest. Dermatol. 99, 870-2.
Yang, M. & Kurkinen, M. (1994) Different mechanisms of regulation of the human stromelysin and collagenase genes. Analysis by a reverse transcription-coupled-PCR assay. Eur. J. Biochem. 222, 651-8.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tsukifuji, R., Sakai, Y., Hatamochi, A. et al. Gene expression of matrix metalloproteinase-1 (interstitial collagenase) and matrix metalloproteinase-3 (stromelysin-1) in basal cell carcinoma by in situ hybridization using chondroitin ABC lyase. J Mol Hist 29, 401–407 (1997). https://doi.org/10.1023/A:1026443018764
Issue Date:
DOI: https://doi.org/10.1023/A:1026443018764