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.
"In tumors, the glycosylation of SLRPs may vary between and within individual tumors [21,33-35]. The difference between normal human OPTC (45–50 kDa) and CLL-derived OPTC (37 kDa) may be due to differences in glycosylation. "
[Show abstract][Hide abstract] ABSTRACT: Opticin (OPTC) is a member of the small leucine-rich proteoglycan (SLRP) family and is localized particularly in certain extracellular matrices. We have previously reported the unique expression of another SLRP, fibromodulin (FMOD) in the leukemic cells of patients with chronic lymphocytic leukemia (CLL). OPTC is located in the same region as FMOD on chromosome 1 (1q32.1). Cluster up-regulation of genes may be observed in malignancies and the aim of the present study was to analyze the expression of OPTC in CLL cells.
The expression of OPTC was tested by RT-PCR and realtime qPCR in PBMC from CLL patients, other hematological malignancies and healthy controls. The presence of OPTC protein, and its subcellular localization, was investigated using fractionation methods where the obtained lysate fractions were analyzed by Western blotting. Deglycosylation experiments were performed to investigate the glycosylation status of the CLL OPTC.
OPTC was expressed at the gene level in all patients with CLL (n = 90) and in 2/8 patients with mantle cell lymphoma (MCL) but not in blood mononuclear cells of healthy control donors (n = 20) or in tumor samples from nine other types of hematological malignancies. OPTC was detected by Western blot in all CLL samples analyzed (n = 30) but not in normal leukocytes (n = 10). Further analysis revealed a CLL-unique unglycosylated 37 kDa core protein that was found to be located preferentially in the cell nucleus and endoplasmic reticulum (ER) of the CLL cells.
A 37 kDa unglycosylated OPTC protein was detected in ER and in the nucleus of CLL cells and not in healthy control donors. The function of this OPTC core protein remains unclear but its CLL-specific expression and subcellular localization warrants further investigations in the pathobiology of CLL.
"Several studies have demonstrated abnormal expression of the matrix-secreted proteoglycans versican and decorin in various cancer types such as prostate [18,19], breast [20,21], gastric , colorectal [23,24], ovarian , pancreatic , laryngeal [27,28] and testicular tumors . Versican is synthesized mainly by stromal cells and is capable to regulate tumor cell growth and motility. "
[Show abstract][Hide abstract] ABSTRACT: Mammographic density (MD) and malignant-appearing microcalcifications (MAMCs) represent the earliest mammographic findings of non-palpable breast carcinomas. Matrix proteoglycans versican and decorin are frequently over-expressed in various malignancies and are differently involved in the progression of cancer. In the present study, we have evaluated the expression of versican and decorin in non-palpable breast carcinomas and their association with high risk mammographic findings and tumor characteristics.
Three hundred and ten patients with non-palpable suspicious breast lesions, detected during screening mammography, were studied. Histological examination was carried out and the expression of decorin, versican, estrogen receptor α (ERα), progesterone receptor (PR) and c-erbB2 (HER-2/neu) was assessed by immunohistochemistry.
Histological examination showed 83 out of 310 (26.8%) carcinomas of various subtypes. Immunohistochemistry was carried out in 62/83 carcinomas. Decorin was accumulated in breast tissues with MD and MAMCs independently of the presence of malignancy. In contrast, versican was significantly increased only in carcinomas with MAMCs (median ± SE: 42.0 ± 9.1) and MD (22.5 ± 10.1) as compared to normal breast tissue with MAMCs (14.0 ± 5.8), MD (11.0 ± 4.4) and normal breast tissue without mammographic findings (10.0 ± 2.0). Elevated levels of versican were correlated with higher tumor grade and invasiveness in carcinomas with MD and MAMCs, whereas increased amounts of decorin were associated with in situ carcinomas in MAMCs. Stromal deposition of both proteoglycans was related to higher expression of ERα and PR in tumor cells only in MAMCs.
The specific accumulation of versican in breast tissue with high MD and MAMCs only in the presence of malignant transformation and its association with the aggressiveness of the tumor suggests its possible use as molecular marker in non-palpable breast carcinomas.
BMC Cancer 07/2011; 11(1):314. DOI:10.1186/1471-2407-11-314 · 3.36 Impact Factor
"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 . "
[Show abstract][Hide abstract] 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.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.