Introduction. Oral squamous cell carcinoma (OSCC) is one of the ten most common cancers affecting the human population. Tumor pathogenesis implies a multistep process in which cells acquire features that enable them to become tumorigenic and ultimately malignant. The process of OSCC carcinogenesis can be reproduced in animal models, the OSCC induction with 4-nitroquinoline-1-oxide (4NQO) in mice is a widely used tool for studying tumor pathogenesis. Objective. The aim of the present study was to determine the progressive changes in basal lamina and connective tissue remodeling during 4NQO-induced OSCC carcinogenesis. Material and Methods. Samples were classified according to “International Histological Classification of tumors” in mild, moderate, and severe dysplasia and invasive carcinoma. Five samples of each pathologic entity and control healthy tongues were used. Immunohistochemical analysis of collagen IV as well as histochemical analysis of glycosylated molecules (PAS) and collagen I (Picro Sirius red) were performed. Results. During experimental-induced carcinogenesis by 4NQO a progressive basal lamina destruction and collagen I disorganization in adjacent connective tissue can be observed. Conclusion. Our results confirm previous studies that show alterations in extracellular matrix (ECM) in malignant lesions, validating the experimental carcinogenesis induced by 4NQO. 1. Introduction Squamous cell carcinoma of the oral cavity (OSCC) is one of the ten most common tumors affecting the human population [1]. Continued population growth and aging have contributed to the increase in this type of pathology, making it an important public health problem. It starts as an epithelial dysplasia and is characterized by an altered proliferation of squamous dysplastic cells of the epithelial surface stratum [2]. It progresses to degrade the subepithelial basement membrane [2, 3], generating a local destruction and distant invasion through the process of metastasis [3–5]. Local invasion of the underlying connective tissue occurs through islets and cords of epithelial cells [3, 6]. Interaction between tumor cells and extracellular matrix (ECM) components is essential for tumor growth [7, 8] and for the onset of cell spreading and subsequent metastatic activity [9]. The basal lamina, a physicochemical barrier to tumor invasion [10], plays a fundamental role in the processes described above. It is a highly specialized structure, consisting of a set of molecules with different sensitivity to proteolytic degradation. Its components are synthesized and secreted by
References
[1]
P. Riera and B. Martinez, “Mortalidad y morbilidad por cancer oral y faringeo en Chile,” Revista Médica de Chile, vol. 133, pp. 555–563, 2005.
[2]
D. D. Dantas, C. C. Ramos, A. L. Costa, L. B. Souza, and L. P. Pinto, “Clinical-pathological parameters in squamous cell carcinoma of the tongue,” Brazilian Dental Journal, vol. 14, no. 1, pp. 22–25, 2003.
[3]
S. Ghosh, H. G. Munshi, R. Sen et al., “Loss of adhesion-regulated proteinase production is correlated with invasive activity in oral squamous cell carcinoma,” Cancer, vol. 95, no. 12, pp. 2524–2533, 2002.
[4]
D. Hanahan and J. Folkman, “Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis,” Cell, vol. 86, no. 3, pp. 353–364, 1996.
[5]
D. Hanahan and R. A. Weinberg, “The hallmarks of cancer,” Cell, vol. 100, no. 1, pp. 57–70, 2000.
[6]
H. K. Williams, “Molecular pathogenesis of oral squamous carcinoma,” Journal of Clinical Pathology, vol. 53, no. 4, pp. 165–172, 2000.
[7]
L. A. Liotta, “Tumor invasion and metastases: role of the basement membrane: Warner-Lambert Parke-Davis award lecture,” American Journal of Pathology, vol. 117, no. 3, pp. 340–348, 1984.
[8]
D. F. Wilson, J. De-Jun, A. M. Pierce, and O. W. Wiebkin, “Oral cancer: role of the basement membrane in invasion,” Australian Dental Journal, vol. 44, no. 2, pp. 93–97, 1999.
[9]
A. Fenyvesi, “The prognostic significance of type IV collagen expression in colorectal carcinomas,” Archive of Oncology, vol. 11, no. 2, pp. 65–70, 2003.
[10]
J. A. Engbring and H. K. Kleinman, “The basement membrane matrix in malignancy,” Journal of Pathology, vol. 200, no. 4, pp. 465–470, 2003.
[11]
A. L. A. Pereira, S. S. L. Veras, E. Silveira et al., “The role of extracellular proteins matrix and the metalloproteinases in head and neck carcinomas: an update review,” Revista Brasileira de Otorrinolaringologia, vol. 71, no. 1, pp. 81–86, 2005.
[12]
M. Hilska, Y. Collan, J. Peltonen, R. Gullichsen, H. Paajanen, and M. Laato, “The distribution of collagen types I, III, and IV in normal and malignant colorectal mucosa,” European Journal of Surgery, vol. 164, no. 6, pp. 457–464, 1998.
[13]
B. Neville, D. Damm, C. Allen, and J. Bouquot, Oral and Maxillofacial Pathology, Sauders-Elsevier, 3rd edition, 2009.
[14]
C. Catusse, M. Polette, C. Coraux, H. Burlet, and P. Birembaut, “Modified basement membrane composition during bronchopulmonary tumor progression,” Journal of Histochemistry and Cytochemistry, vol. 48, no. 5, pp. 663–669, 2000.
[15]
X. H. Tang, B. Knudsen, D. Bemis, S. Tickoo, and L. J. Gudas, “Oral cavity and esophageal carcinogenesis modeled in carcinogen-treated mice,” Clinical Cancer Research, vol. 10, no. 1 I, pp. 301–313, 2004.
[16]
T. Nunoshiba and B. Demple, “Potent intracellular oxidative stress exerted by the carcinogen 4- nitroquinoline-N-oxide,” Cancer Research, vol. 53, no. 14, pp. 3250–3252, 1993.
[17]
E. Olfert, B. Cross, and A. McWilliam, Guide to the Care and Use of Experimental Animals, vol. 1, Canadian Council on Animal Care, Ottawa, Ontario, Canada, 1999.
[18]
L. C. U. Junqueira, G. Bignolas, and R. R. Brentani, “Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections,” Histochemical Journal, vol. 11, no. 4, pp. 447–455, 1979.
[19]
J. Duaso, G. Rojo, G. Cabrera et al., “Trypanosoma cruzi induces tissue disorganization and destruction of chorionic villi in an ex vivo infection model of human placenta,” Placenta, vol. 31, no. 8, pp. 705–711, 2010.
[20]
P. Boyle and B. Levin, “World Cancer Report,” in World Health Organization, vol. 10, pp. 331–336, IARC Press, Lyon, France, 2008.
[21]
H. C. Burck, Histologische Technik: Leitfaden für de Herstellung mikroskopischer Pr?parate in Unterricht und Praxis, Georg Thieme, New York, NY, USA, 5th edition, 1982.
[22]
Y. Chen, E. Sasatomi, T. Satoh, K. Miyazaki, and O. Tokunaga, “Abnormal distribution of collagen type IV in extrahepatic bile duct carcinoma,” Pathology International, vol. 50, no. 11, pp. 884–890, 2000.
[23]
M. Egeblad, M. G. Rasch, and V. M. Weaver, “Dynamic interplay between the collagen scaffold and tumor evolution,” Current Opinion in Cell Biology, vol. 22, no. 5, pp. 697–706, 2010.
[24]
W. P. Daley, S. B. Peters, and M. Larsen, “Extracellular matrix dynamics in development and regenerative medicine,” Journal of Cell Science, vol. 121, no. 3, pp. 255–264, 2008.
[25]
H. J?rvel?inen, A. Sainio, M. Koulu, T. N. Wight, and R. Penttinen, “Extracellular matrix molecules: potential targets in pharmacotherapy,” Pharmacological Reviews, vol. 61, no. 2, pp. 198–223, 2009.
[26]
M. Allen and J. L. Jones, “Jekyll and Hyde: the role of the microenvironment on the progression of cancer,” Journal of Pathology, vol. 223, no. 2, pp. 162–176, 2011.
[27]
C. A. Rivera, D. A. Droguett, U. Kemmerling, and B. A. Venegas, “Chronic restraint stress in oral squamous cell carcinoma,” Journal of Dental Research, vol. 90, no. 6, pp. 799–803, 2011.
[28]
G. Botelho, R. Almeida, and T. Correia, “Collagen type I ex pression in squa mous cell carcinoma of the oral cavity,” Pesquisa Odontológica Brasileira, vol. 17, no. 1, pp. 82–88, 2003.