Abstract
Mast cells are a significant source of tumor necrosis factor (TNF) superfamily members, such as TNF-α, CD30 ligand/CD153 (CD30L) and CD40L/CD154. Furthermore, the expression of some of these proteins in mast cells has been associated with tumorigenesis, and mast cells have been found to be increased in number in the basal cell carcinoma (BCC) lesion. In this study, we have examined the expression of TNF-α, CD30L and CD40L immunoreactivity in mast cells in the healthy-looking skin and lesional skin of ten patients with superficial spreading BCC. Also, the counterparts of these molecules, TNF receptor (TNFR) I and II as well as CD30 and CD40, were analysed immunohistochemically. We found that numbers of mast cells and Kit-positive cells were significantly increased in the dermal BCC lesion. The percentage of CD30L-positive mast cells and the number of CD30-positive cells were significantly increased in the upper dermis of the BCC lesion as well. In addition, the numbers of TNF-α-positive mast cells and cells with TNFRI and TNFRII were markedly increased in the upper lesional dermis. In contrast, no mast cells positive for CD40L could be detected, even though the lesional dermis contained increased numbers of CD40 positive cells. The BCC epithelium was positive for TNFRI, TNFRII and CD40, but not for CD30, though the larger basal buds appeared to be less intensely stained for TNFRI and CD40. In conclusion, mast cells positive for CD30L and TNF-α, but not CD40L, are increased in number in the lesional dermis in BCC. These data suggest plausible pathways whereby mast cells can be activated and to interact with other cells and thereby contribute to the tumorigenesis in BCC.
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Ackermann L, Harvima IT (1998) Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis. Arch Dermatol Res 290:353–359
Ackermann L, Harvima IT, Pelkonen J, Ritamäki-Salo V, Naukkarinen A, Harvima RJ, Horsmanheimo M (1999) Mast cells in psoriatic skin are strongly positive for interferon-gamma. Br J Dermatol 140:624–633
Aoki M, Pawankar R, Niimi Y, Kawana S (2003) Mast cells in basal cell carcinoma express VEGF, IL-8 and RANTES. Int Arch Allergy Immunol 130:216–223
Bengtsson Å (2001) The role of CD30 in atopic disease. Allergy 56:593–603
Ch’ng S, Wallis RA, Yuan L, Davis PF, Tan ST (2006) Mast cells and cutaneous malignancies. Mod Pathol 19:149–159
Dimitriadou V, Koutsilieris M (1997) Mast cell-tumor cell interactions: for or against tumor growth and metastasis? Anticancer Res 17:1541–1550
Fischer M, Harvima IT, Carvalho RFS, Möller C, Naukkarinen A, Enblad G, Nilsson G (2006) Mast cell CD30 ligand is up-regulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion. J Clin Invest 116:2748–2756
Galli SJ, Nakae S, Tsai M (2005) Mast cells in the development of adaptive immune responses. Nat Immunol 6:135–142
Gibbs BF, Wierecky J, Welker P, Henz BM, Wolff HH, Grabbe J (2001) Human skin mast cells rapidly release preformed and newly generated TNF-α and IL-8 following stimulation with anti-IgE and other secretagogues. Exp Dermatol 10:312–320
Grimbaldeston MA, Skov L, Baadsgaard O, Skov BG, Marshman G, Finlay-Jones JJ, Hart PH (2000) High dermal mast cell prevalence is a predisposing factor for basal cell carcinoma in humans. J Invest Dermatol 115:317–320
Grimbaldeston MA, Skov L, Finlay-Jones JJ, Hart PH (2002) Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans. Methods 28:90–96
Henz BM, Maurer M, Lippert U, Worm M, Babina M (2001) Mast cells as initiators of immunity and host defense. Exp Dermatol 10:1–10
Hjertson M, Kivinen PK, Dimberg L, Nilsson K, Harvima IT, Nilsson G (2003) Retinoic acid inhibits in vitro-development of mast cells but has no marked effect on mature human skin tryptase- and chymase-positive mast cells. J Invest Dermatol 120:239–245
Horsmanheimo L, Harvima IT, Järvikallio A, Harvima RJ, Naukkarinen A, Horsmanheimo M (1994) Mast cells are one major source of interleukin-4 in atopic dermatitis. Br J Dermatol 131:348–353
Humphreys TR, Monteiro MR, Murphy GF (2000) Mast cells and dendritic cells in basal carcinoma stroma. Dermatol Surg 26:200–203
Huttunen M, Naukkarinen A, Horsmanheimo M, Harvima IT (2002) Transient production of stem cell factor in dermal cells but increasing expression of Kit receptor in mast cells during normal wound healing. Arch Dermatol Res 294:324–330
Janowski P, Strzelecki M, Brzezinska-Blaszczyk E, Zalewska A (2001) Computer analysis of normal and basal cell carcinoma mast cells. Med Sci Monit 7:260–265
Kashiwakura J, Yokoi H, Saito H, Okayama Y (2004) T cell proliferation by direct cross-talk between OX40 ligand on human mast cells and OX40 on human T cells: comparison of gene expression profiles between human tonsillar and lung-cultured mast cells. J Immunol 173:5247–5257
Kooy AJW, Prens EP, van Heukelum A, Vuzevski VD, van Joost T, Tank B (1999) Interferon-γ-induced ICAM-1 and CD40 expression, complete lack of HLA-DR and CD80 (B7.1), and inconsistent HLA-ABC expression in basal cell carcinoma: a possible role for interleukin-10? J Pathol 187:351–357
Kristensen M, Chu CQ, Eedy DJ, Feldmann M, Brennan FM, Breathnach SM (1993) Localization of tumour necrosis factor-alpha (TNF-α) and its receptors in normal and psoriatic skin: epidermal cells express the 55-kD but not the 75-kD TNF receptor. Clin Exp Immunol 94:354–362
Malejczyk M, Jozwiak J, Jablonska S, Pfister H, Majewski S, Malejczyk J (2005) Circulating soluble tumour necrosis factor receptors in patients with epidermodysplasia verruciformis as compared to patients with cutaneous tumours in the general population. Oncol Rep 13:151–155
Marshall JS, Jawdat DM (2004) Mast cells in innate immunity. J Allergy Clin Immunol 114:21–27
Molin D, Fischer M, Xiang Z, Larsson U, Harvima I, Venge P, Nilsson K, Sundström C, Enblad G, Nilsson G (2001) Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin’s disease. Br J Haematol 114:616–623
Ohta Y, Hamada Y (2004) In situ expression of CD40 and CD40 ligand in psoriasis. Dermatology 209:21–28
Ottaiano A, Pisano C, De Chiara A, Ascierto PA, Botti G, Barletta E, Apice G, Gridelli C, Iaffaioli VR (2002) CD40 activation as potential tool in malignant neoplasms. Tumori 88:361–366
Pasch MC, Timár KK, van Meurs M, Heydendael VMR, Bos JD, Laman JD, Asghar SS (2004) In situ demonstration of CD40- and CD154-positive cells in psoriatic lesions and keratinocyte production of chemokines by CD40 ligation in vitro. J Pathol 203:839–848
Pawankar R, Okuda M, Yssel H, Okumura K, Ra C (1997) Nasal mast cells in perennial allergic rhinitis exhibit increased expression of the FcɛRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells. J Clin Invest 99:1465–1466
Poniecka AW, Alexis JB (1999) An immunohistochemical study of basal cell carcinoma and trichoepithelioma. Am J Dermatopathol 21:332–336
Rossi FM, Degan M, Mazzocut-Zecchin L, Di Francia R, Aldinucci D, Pinto A, Gattei V (2001) CD30L up-regulates CD30 and IL-4 expression by T cells. FEBS Lett 508:418–422
Skov L, Allen MH, Bang B, Francis D, Barker JN, Baadsgaard O (2003) Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF-alpha polymorphism at position-308. Exp Dermatol 12:772–776
Tamada K, Chen L (2006) Renewed interest in cancer immunotherapy with the tumor necrosis factor superfamily molecules. Cancer Immunol Immunother 55:355–362
Viac J, Schmitt D, Claudy A (1997) CD40 expression in epidermal tumors. Anticancer Res 17:569–572
Weber A, Maurer M (2005) Skin site mast cell numbers correlate with rates of nodular growth, but not incidence, of basal cell carcinoma. Dermatology 211:298–299
Wiley SR, Goodwin RG, Smith CA (1996) Reverse signaling via CD30 ligand. J Immunol 157:3635–3639
Yamamoto T, Katayama I, Nishioka K (1997) Expression of stem cell factor in basal cell carcinoma. Br J Dermatol 137:709–713
Acknowledgments
The authors wish to thank the Marie Curie Mobility Actions for Early Stage Researcher by the sixth framework of the EU commission (project no. 504926) and Kuopio University Hospital for financing this study. Ms. Anne Koivisto is acknowledged for expert technical assistance.
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Diaconu, NC., Kaminska, R., Naukkarinen, A. et al. Increase in CD30 ligand/CD153 and TNF-α expressing mast cells in basal cell carcinoma. Cancer Immunol Immunother 56, 1407–1415 (2007). https://doi.org/10.1007/s00262-007-0290-7
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DOI: https://doi.org/10.1007/s00262-007-0290-7