‘Malignant melanoma microecosystem’: Immunohistopathological insights into the stromal cell phenotype (Review)

Quatresooz,Pascale; Reginster,Marie-Annick; Piérard,Gérald  E.

doi:10.3892/etm.2011.221

‘Malignant melanoma microecosystem’: Immunohistopathological insights into the stromal cell phenotype (Review)

Authors:
- Pascale Quatresooz
- Marie-Annick Reginster
- Gérald E. Piérard
View Affiliations

Affiliations: Department of Dermatopathology, University Hospital of Liège, BE-4000 Liège, Belgium
Published online on: February 28, 2011 https://doi.org/10.3892/etm.2011.221
Pages: 379-384

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cutaneous malignant melanoma (MM) is rooted in the dermal connective tissue, which consists of apparently unremarkable stromal cells as they appear upon regular histopathological examination. However, a number of in vitro studies have shown that these cells produce diverse types of cytokines, growth factors and enzymes in excess. In addition, they store and probably release various structural components of the extracellular matrix (ECM). Most of the current information comes from in vitro experiments, and these findings do not always correlate with investigations carried out using excised human MM tissue. The MM-stroma connection appears crucial to the regulation of neoplastic growth, invasiveness and initial metastatic spread. However, little is known about the in vivo intracellular storage and extracellular deposits of specific ECM macromolecules located inside and around MM lesions. This review summarizes various distinct features of the peri-MM stroma, which shows an intracytoplasmic abundance of Factor XIIIa, versican and various α (IV) collagen chains. The area exhibiting such changes corresponds to the location where neoangiogenesis commonly develops and where extravascular unicellular metastatic MM lesions are possibly found. Some of these inconspicuous migratory malignant melanocytes may actually correspond to MM stem cells. Their presence was found to be significantly associated with an increased risk for distant metastases, particularly in the sentinel lymph nodes. Although much remains to be learned, active intervention of the ECM appears likely in the inconspicuous early dermal metastatic migration of MM cells.

View Figures

View References

1.	Dean M, Fojo T and Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 5:275–284. 2005. View Article : Google Scholar
2.	Quatresooz P and Piérard GE: Malignant melanoma: from cell kinetics to micrometastases. Am J Clin Dermatol. Dec 13–2010.(E-pub ahead of print).
3.	Smolle J, Hofmann-Wellenhof R and Fink-Puches R: Melanoma and stroma: an interaction of biological and prognostic importance. Semin Cutan Med Surg. 15:326–335. 1996. View Article : Google Scholar : PubMed/NCBI
4.	Bennett DC: Ultraviolet wavebands and melanoma initiation. Pigment Cell Melanoma Res. 21:520–524. 2008. View Article : Google Scholar : PubMed/NCBI
5.	Brenner M, Degitz K, Besch R and Berking C: Differential expression of melanoma-associated growth factors in keratinocytes and fibroblasts by ultraviolet A and ultraviolet B radiation. Br J Dermatol. 153:733–739. 2005. View Article : Google Scholar : PubMed/NCBI
6.	Philips N, Keller T and Holmes C: Reciprocal effects of ascorbate on cancer cell growth and the expression of matrix metalloproteinases and transforming growth factor-beta. Cancer Lett. 256:49–55. 2007. View Article : Google Scholar : PubMed/NCBI
7.	Philips N, Conte J, Chen YJ, Natrajan P, Taw M, Keller T, Givant J, Tuason M, Dulaj L, Leonardi D and Gonzalez S: Beneficial regulation of matrix-metalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-β by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet-radiated fibroblasts, and melanoma cells. Arch Dermatol Res. 301:487–495. 2009.
8.	Dvorak HF: Tumors: wounds that do not heal. N Engl J Med. 315:1650–1659. 1986. View Article : Google Scholar : PubMed/NCBI
9.	De Wever O and Mareel M: Role of tissue stroma in cancer cell invasion. J Pathol. 200:429–447. 2003.PubMed/NCBI
10.	Quatresooz P, Piérard-Franchimont C, Paquet P and Piérard GE: Angiogenic fast-growing melanomas and their micrometastases. Eur J Dermatol. 20:302–307. 2010.PubMed/NCBI
11.	Piérard GE and Piérard-Franchimont C: Stochastic relationship between the growth fraction and vascularity of thin malignant melanomas. Eur J Cancer. 33:1888–1892. 1997.PubMed/NCBI
12.	Piérard-Franchimont C, Henry F, Heymans O and Piérard GE: Vascular retardation in dormant growth-stunted malignant melanomas. Int J Mol Med. 4:403–406. 1999.PubMed/NCBI
13.	Wernert N: The multiple roles of tumour stroma. Virchows Arch. 430:433–443. 1997. View Article : Google Scholar : PubMed/NCBI
14.	Liotta LA and Kohn EC: The microenvironment of the tumour-host interface. Nature. 411:375–379. 2001. View Article : Google Scholar : PubMed/NCBI
15.	Dingemans KP, Zeeman-Boeschoten IM, Keep RF and Das PK: Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype. Int J Cancer. 54:1010–1016. 1993. View Article : Google Scholar : PubMed/NCBI
16.	Lugassy C and Barnhill RL: Angiotropic malignant melanoma and extravascular migratory metastasis: description of 26 cases with emphasis on a new mechanism of tumor spread. Pathology. 36:485–490. 2004. View Article : Google Scholar : PubMed/NCBI
17.	Claessens N, Piérard GE, Piérard-Franchimont C, Arrese JE and Quatresooz P: Immunohistochemical detection of incipient melanoma micrometastases. Relationship with sentinel lymph node involvement. Melanoma Res. 15:107–110. 2005. View Article : Google Scholar : PubMed/NCBI
18.	Lugassy C and Barnhill RL: Angiotropic melanoma and extravascular migratory metastasis. A review. Adv Anat Pathol. 14:195–201. 2007. View Article : Google Scholar : PubMed/NCBI
19.	Quatresooz P, Piérard GE, Piérard-Franchimont C, Humbert P and Piérard S: Introduction to the spectral analysis of microvasculature in primary cutaneous melanoma. Pathol Biol. Feb;2010.(E-pub ahead of print).
20.	Quatresooz P, Arrese JE, Piérard-Franchimont C and Piérard GE: Immunohistochemical aid at risk stratification of melanocytic neoplasms. Int J Oncol. 24:211–216. 2004.PubMed/NCBI
21.	Quatresooz P, Piérard-Franchimont C and Piérard GE: Highlighting the immunohistochemical profile of melanocytomas. Oncol Rep. 19:1367–1372. 2008.PubMed/NCBI
22.	Quatresooz P, Piérard GE and Piérard-Franchimont C; the Mosan Study Group of Pigmented Tumors: Molecular pathways supporting the proliferation staging of malignant melanoma. Int J Mol Med. 24:295–301. 2009.PubMed/NCBI
23.	Quatresooz P, Piérard-Franchimont C and Piérard GE; the Mosan Study Group of Pigmented Tumors: Molecular histology on the diagnostic cutting edge between malignant melanomas and cutaneous melanocytomas. Oncol Rep. 22:1263–1267. 2009.PubMed/NCBI
24.	Piérard-Franchimont C, Arrese JE, Nikkels AF, Al Saleh W, Delvenne P and Piérard GE: Factor XIIIa-positive dermal dendrocytes and proliferative activity of cutaneous cancers. Virchows Arch. 429:43–48. 1996.
25.	Schatton T and Franck MH: Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res. 21:39–55. 2007. View Article : Google Scholar
26.	Rappa G, Fodstad O and Lorico A: The stem cell-associated antigen CD133 (Prominin-1) is a molecular therapeutic target for metastatic melanoma. Stem Cells. 26:3008–3017. 2008. View Article : Google Scholar : PubMed/NCBI
27.	Schatton T, Murphy GF, Frank NY, et al: Identification of cells initiating human melanomas. Nature. 451:345–349. 2008. View Article : Google Scholar : PubMed/NCBI
28.	Cramer SF: Stem cells for epidermal melanocytes. A challenge for students of dermatopathology. Am J Dermatopathol. 31:331–341. 2009. View Article : Google Scholar : PubMed/NCBI
29.	Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, van Belle PA, Xu X, Elder DE and Herlyn M: A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 65:9328–9337. 2005. View Article : Google Scholar : PubMed/NCBI
30.	Grichnik JM, Burch JA, Schulteis RD, Shan S, Liu J, Darrow TL, Vervaert CE and Seigler HF: Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol. 126:142–153. 2006. View Article : Google Scholar : PubMed/NCBI
31.	Buac K and Pavan WJ: Stem cells of the melanocyte lineage. Cancer Biomark. 3:203–209. 2007.PubMed/NCBI
32.	Klein WM, Wu BP, Zhao S, Wu H, Klein-Szanto AJ and Tahan SR: Increased expression of stem cell markers in malignant melanoma. Mod Pathol. 20:102–107. 2007. View Article : Google Scholar : PubMed/NCBI
33.	Arrese Estrada J and Piérard GE: Factor XIIIa-positive dendrocytes and the dermal microvascular unit. Dermatologica. 180:51–53. 1990.PubMed/NCBI
34.	Quatresooz P, Paquet P, Hermanns-Lê T and Pierard GE: Molecular mapping of Factor XIIIa-enriched dendrocytes in the skin. Int J Mol Med. 22:403–409. 2008.PubMed/NCBI
35.	Quatresooz P and Piérard GE: Immunohistochemical clues at aging of the skin microvascular unit. J Cutan Pathol. 36:39–43. 2009. View Article : Google Scholar : PubMed/NCBI
36.	Fullen DR and Headington JT: Factor XIIIa-positive dermal dendritic cells and HLA-DR expression in radial versus vertical growth-phase melanomas. J Cutan Pathol. 25:553–558. 1998. View Article : Google Scholar : PubMed/NCBI
37.	Denton KJ, Cotton DW, Wright A and Hird P: Factor XIIIa in nodular malignant melanoma and Spitz naevi. Br J Dermatol. 12:783–786. 1990.PubMed/NCBI
38.	Polak ME, Johnson P, Di Palma S, Higgins B, Hurren J, Borthwick NJ, Jager MJ, Mccormick D and Cree IA: Presence and maturity of dendritic cells in melanoma lymph node metastases. J Pathol. 207:83–90. 2005. View Article : Google Scholar : PubMed/NCBI
39.	Lugassy C, Eyden BP, Christensen L and Escande JP: Angiotumoral complex in human malignant melanoma characterized by free laminin: ultrastructural and immunohistochemical observations. J Submicrosc Cytol Pathol. 29:19–28. 1997.
40.	Schaumburg-Lever G, Lever I, Fehrenbacher B, Möller H, Bischof B, Kaiserling E, Garbe C and Rassner G: Melanocytes in naevi and melanomas synthesize basement membrane and basement membrane-like material. An immunohistochemical and electron microscopic study including immunoelectron microscopy. J Cutan Pathol. 27:67–75. 2000. View Article : Google Scholar
41.	Van Duinen CM, Fleuren GJ and Bruijn JA: The extracellular matrix in pigmented skin lesions: an immunohistochemical study. Histopathology. 24:33–40. 1994.PubMed/NCBI
42.	Lugassy C, Kickersin GR, Christensen L, Karaoli T, Le Charpeniter M, Escande JP and Barnhill RL: Ultrastructural and immunohistochemical studies of the periendothelial matrix in malignant melanoma: evidence for an amorphous matrix containing laminin. J Cutan Pathol. 26:78–83. 1999. View Article : Google Scholar
43.	Lugassy C, Shahsafaei A, Bonitz P, Busam KJ and Barnhill RL: Tumor microvessels in melanoma express the beta-2 chain of laminin. Implications for melanoma metastasis. J Cutan Pathol. 26:222–226. 1999. View Article : Google Scholar : PubMed/NCBI
44.	Quatresooz P and Piérard GE: Immunohistochemical investigation of α 1 (IV) and α 5 (IV) collagen chains in a broad spectrum of melanocytic tumours. Melanoma Res. 15:161–168. 2005.
45.	Wight TN: Versican: a versatile extracellular matrix proteoglycan in cell biology. Curr Opin Cell Biol. 14:617–623. 2002. View Article : Google Scholar : PubMed/NCBI
46.	Serra M, Miquel L, Domenzain C, Docampo MJ, Fabra A, Wight TN and Bassols A: V3 versican isoform expression alters the phenotype of melanoma cells and their tumorigenic potential. Int J Cancer. 114:879–886. 2005. View Article : Google Scholar : PubMed/NCBI
47.	Touab M, Villena J, Barranco C, Arumi-Uria M and Bassols A: Versican is differentially expressed in human melanoma and may play a role in tumor development. Am J Pathol. 160:549–557. 2002. View Article : Google Scholar : PubMed/NCBI
48.	Docampo MJ, Rabanal RM, Miquel-Serra L, Hernandez D, Domenzain C and Bassols A: Altered expression of versican and hyaluronan in melanocytic tumors of dogs. Am J Vet Res. 68:1376–1385. 2007. View Article : Google Scholar : PubMed/NCBI
49.	Gambichler T, Kreuter A, Grothe S, Altmeyer P, Brockmeyer HN and Rotterdam S: Versican overexpression in cutaneous malgnant melanoma. Eur J Med Res. 13:500–504. 2008.PubMed/NCBI
50.	Seité S, Moyal D, Richard S, de Rigal J, Lévêque JL, Hourseau C and Fourtanier A: Effects of repeated suberythemal doses of UVA in human skin. Eur J Dermatol. 7:204–209. 1997.
51.	Seité S, Zucchi H, Septier D, Igondjo-Tchen S, Senni K and Godeau G: Elastin changes during chronological and photo-ageing: the important role of lysozyme. J Eur Acad Dermatol Venereol. 20:980–987. 2006.PubMed/NCBI
52.	Piérard-Franchimont C, Uhoda I, Saint Léger D and Piérard GE: Androgenic alopecia and stress-induced premature senescence by cumulative ultraviolet light exposure. Exog Dermatol. 1:203–206. 2002.
53.	Muto J, Kuroda K, Wachi H, Hirose S and Tajima S: Accumulation of elafin in actinic elastosis of sun-damaged skin: elafin binds to elastin and prevents elastolytic degradation. J Invest Dermatol. 127:1358–1366. 2007. View Article : Google Scholar : PubMed/NCBI
54.	Williams SE, Brown TI, Roghanian A and Sallenave JM: SLPI and elafin: one glove, many fingers. Clin Sci. 110:21–35. 2006. View Article : Google Scholar : PubMed/NCBI
55.	Nozowa F, Hirota M, Okabe A, Shibata M, Iwamura T, Haga Y and Ogawa M: Elastase activity enhances the adhesion of neutrophil and cancer cells to vascular endothelial cells. J Surg Res. 94:153–158. 2000. View Article : Google Scholar : PubMed/NCBI
56.	Yu KS, Lee Y, Kim CM, Park EC, Choi J, Lim DS, Chung YH and Koh SS: The protease inhibitor, elafin, induces p53-dependent apoptosis in human melanoma cells. Int J Cancer. 127:1308–1320. 2010.PubMed/NCBI
57.	Kamsteeg M, Jansen PA, van Vlijmen-Willems IM, van Erp PE, Rodij-Olthuis D, van der Valk PG, Feuth T, Zeeuwen PL and Schalkwijk J: Molecular diagnostics of psoriasis, atopic dermatitis, allergic contact dermatitis and irritant contact dermatitis. Br J Dermatol. 162:568–578. 2010. View Article : Google Scholar : PubMed/NCBI
58.	Paczesny S, Braun TM, Levine JE, et al: Elafin is a biomarker of graft-versus-host disease of the skin. Sci Transl Med. 2:13ra22010. View Article : Google Scholar : PubMed/NCBI
59.	Marcoval J, Moreno A, Graells J, Vidal A, Escriba JM, Garcia-Ramirez JM and Fabra A: Angiogenesis and malignant melanoma. Angiogenesis is related to the development of vertical (tumorigenic) growth phase. J Cutan Pathol. 24:212–218. 1997. View Article : Google Scholar : PubMed/NCBI
60.	Alonso S, Ortiz P, Pollan M, Pérez-Gomez B, Sanchez L, Acuna MJ, Pajares R, Martinez-Tello FJ, Hortelano CM, Piris MA and Rodriguez-Peralto JL: Progression in cutaneous malignant melanoma is associated with distinct expression profiles. A tissue microarray-based study. Am J Pathol. 164:193–203. 2004. View Article : Google Scholar : PubMed/NCBI
61.	Fecher LA, Cummings SD, Keefe MJ and Alani RM: Toward a molecular classification of melanoma. J Clin Oncol. 25:1606–1620. 2007. View Article : Google Scholar : PubMed/NCBI
62.	Plaza JA, Suster D and Perez-Montiel D: Expression of immunohistochemical markers in primary and metastatic malignant melanoma: a comparative study in 70 patients using a tissue microarray technique. Appl Immunohistochem Mol Morphol. 15:421–425. 2007. View Article : Google Scholar
63.	Ohsie SJ, Sarantopoulos GP, Cochran AJ and Binder SW: Immunohistochemical characteristics of melanoma. J Cutan Pathol. 35:433–444. 2008. View Article : Google Scholar
64.	Hamza S: Prognostic parameters of malignant melanoma. Diagn Histopathol. 16:330–336. 2010. View Article : Google Scholar
65.	Schopfer G, Wellbrock C and Marais R: Melanoma biology and new targeted therapy. Nature. 445:851–857. 2007. View Article : Google Scholar : PubMed/NCBI
66.	Piérard GE, Quatresooz P, Rorive A and Piérard-Franchimont C; Groupe Mosan d'Etude des Tumeurs Pigmentaires: Malignant melanoma: conceptual and therapeutic innovations based on translational research. Rev Med Liège. 63:579–584. 2008.PubMed/NCBI
67.	Basu B, Biswas S, Wrigley J, Sirohi B and Corrie P: Angiogenesis in cutaneous malignant melanoma and potential therapeutic strategies. Exp Rev Anticancer The. 9:1583–1598. 2009. View Article : Google Scholar : PubMed/NCBI
68.	Sullivan RJ and Atkins MB: Molecular-targeted therapy in malignant melanoma. Exp Rev Anticancer Ther. 9:567–581. 2009. View Article : Google Scholar : PubMed/NCBI
69.	Kerbel RS, Kobayashi H, Graham CH and Lu C: Analysis and significance of the malignant ‘eclipse’ during the progression of primary cutaneous human melanomas. J Invest Dermatol Symp Proc. 1:183–187. 1996.