The increased accumulation of structurally modified versican and decorin is related with the progression of laryngeal cancer
ABSTRACT Versican and decorin, two proteoglycans (PGs) with contradictory roles in the pathophysiology of cancer, comprise important stromal components in many tumor types and play a crucial role in the progression of cancer. In this study, we provide direct evidence for a significant and stage-related accumulation of versican and decorin in the tumor-associated stroma of laryngeal squamous cell carcinoma (LSCC) in comparison to normal larynx. Both PGs were found to be co-localized within the peritumorous stroma. In addition, the accumulated versican and decorin were markedly modified on both protein core and glycosaminoglycan (GAG) levels. Decorin, which was present under both glycanated and non-glycanated forms, perceptibly increased with the progression of LSCC, compared to the normal larynx. Tumor-associated glycanated decorin was found to contain significant amounts of dermatan sulfate (DS) sequences. Versican was also found to undergo stage-related structural modifications since a marked heterogeneity of protein cores was observed, being intense in late stage of laryngeal cancer. The increased accumulation of both versican and decorin was associated with a significant stage-related increase of the molar ratio of Delta di-mono4S to Delta di-mono6S up to approximately threefold in LSCC compared to the normal ones. The modified chemical structure of both PGs could be associated with the degree of aggressiveness of laryngeal squamous cell carcinomas.
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- "The laryngeal tumor is a rare form of neoplasia representing 2% of all human tumors . Histologically, squamous cell carcinoma (SCC) comprises more than 95% of laryngeal carcinomas and is obviously the most important laryngeal cancer . LSCC, an aggressive and mostly lethal malignancy, is known to be resistant to a number of apoptotic stimuli . "
ABSTRACT: Arsenic trioxide (As(2)O(3)) is used clinically to treat acute promyelocytic leukemia and has activity in vitro against several solid tumor cell lines, where induction of differentiation and apoptosis are the prime effects. As a novel anticancer agent for treatment of solid cancers, As(2)O(3) is promising and the mechanism has been not still fully understood. Laryngeal squamous cell carcinoma (LSCC) is one common tumor in head and neck cancers. The objective of this study was to investigate the effects of As(2)O(3) on LSCC cell line HEP-2, and their possible involvement in As(2)O(3)-induced apoptosis. The cell viability was analyzed by MTT assay method and the morphological changes were observed by an inverted microscope and acridine orange (AO) staining. The caspase-3 activity was measured by a fluorophotometer. The expression of survivin mRNA was evaluated by RT-PCR. In this study, we demonstrated an apoptotic effect of As(2)O(3) in LSCC cell line Hep-2. In Hep-2 cells, As(2)O(3) decreased the cell viability, inhibited the growth and proliferation, induced apoptosis and increased the activity of caspase-3 in a dose-dependent manner. And the expression of survivin mRNA was also decreased in a dose-dependent manner. We concluded that As(2)O(3) induced the apoptosis of Hep-2 cells via down-regulating the expression of survivin mRNA.Auris Nasus Larynx 04/2008; 35(1):95-101. DOI:10.1016/j.anl.2007.07.009 · 1.00 Impact Factor
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ABSTRACT: The major proteoglycan of normal human larynx is aggrecan. In laryngeal carcinoma, aggrecan is depleted, with versican and decorin appearing in higher amounts. Proteoglycans in laryngeal carcinoma samples were characterized immunohistochemically and using Western blotting; their expression was examined by RT-PCR. Aggrecan was totally removed in advanced cancer and its RT-PCR product was not identified. Both versican and decorin were overexpressed in cancer, versican much more than decorin. Decorin expression was higher than that of versican in the normal larynx; therefore, their disproportionate overexpression during cancer resulted in about equimolar expression. Both proteoglycans' expression correlated with their stage-related accumulation within the tissue. These data add to our previous findings and support the view that the levels of expression and the extent of accumulation and localization in the tumor stroma of structurally modified versican and decorin could be associated with the degree of aggressiveness of laryngeal carcinoma.Anticancer research 01/2008; 28(1A):245-51. · 1.87 Impact Factor
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ABSTRACT: D-glucuronyl C5-epimerase (GLCE) is one of the key enzymes in proteoglycan biosynthesis. However, nothing is known about expression and activity of the protein in cancer. In this study, we investigated GLCE expression in human breast cancer using multipex RT-PCR, QRT-PCR and Western-blot assays. In total, 21 patients without malignancy and 74 patients with breast tumor were investigated. The obtained data showed that in 82-84% of human breast tumors there is either downregulation or loss of D-glucuronyl C5-epimerase mRNA expression and significant decrease of the protein content. In most cases (77%), GLCE expression was decreased also in the normal-appearing tissue surrounding the tumor node but the protein amount was comparable to normal breast tissue. These findings represent the first data about involvement of human D-glucuronyl C5-epimerase in malignant transformation.International Journal of Cancer 03/2007; 122(5):1172-6. DOI:10.1002/ijc.23203 · 5.01 Impact Factor