Proteoglycans and WT1 as markers for distinguishing adenocarcinoma, epithelioid mesothelioma, and benign mesothelium

Abstract

Malignant mesothelioma is a tumour frequently accompanied by an effusion with elevated hyaluronan levels. To distinguish malignant mesothelioma, adenocarcinoma, and reactive benign mesothelium with cytological and histological methods including immunocytochemistry is a major diagnostic challenge. The Wilms' tumour susceptibility gene 1 (WT1), expressed during transition of mesenchyme to epithelial tissues, is regarded as a marker for the mesothelial lineage. Its effect on the cell phenotype may be regulated via the syndecans, i.e. proteoglycans on the cell surface. To determine how WT1, proteoglycans, and hyaluronan synthase are expressed in mesothelioma, adenocarcinoma, and reactive benign mesothelium, we studied these molecules at the mRNA and protein levels, with the additional purpose of finding diagnostic parameters. Adenocarcinoma cells produced more mRNA for syndecan-1, but cells derived from mesothelium expressed WT1, biglycan, and larger amounts of syndecan-2. The difference in gene expression of these two syndecans was best monitored by the ratio between them. Syndecan-4 was highly expressed in all malignant cell lines, this expression being 1.7-5 times greater than in benign mesothelial cells. Although hyaluronan synthase-1 and versican could not distinguish between the three conditions, versican expression was associated with a high rate of proliferation. These findings suggest that syndecan-1 and syndecan-2 together may be useful diagnostic markers, with stronger staining for the latter epitope in mesothelial tissues. The alternating appearance of these two syndecans can be shown not only by RT-PCR and FACS in vitro, but also by immunohistochemistry on clinical material.

Expression and prognostic role of syndecan-2 in prostate cancer

“…Moreover, an increased level of SDC2 led to a less adhesive phenotype and loss of contact inhibition. 12,13 These results could point to two conclusions; first, normal colon epithelial cells might acquire SDC2 expression activities during carcinogenesis, and second, expression of SDC2 is necessary for tumourigenic activity. 9,12 SDC2 may function in colon cancer cells by at least two different mechanisms.…”

“…7 Early recognizable role of SDC2 was cell adhesion and migration, but recently SDC2 has also been implicated in the tyrosine kinase signalling pathway activation, cancer progression, and angiogenesis. [8][9][10][11][12] Several studies investigated the role of SDC2 in different carcinomas; [13][14][15] however, only one was focused on SDC2 in prostate cancer. 16 SDC2 expression and relationship with established prognostic features were assessed in a cohort of 86 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma to determine the expression and prognostic value of SDC2 in prostate cancer.…”

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

“…[11][12][13][14] Versican expression promotes tumor growth by destabilizing focal cell contacts, thus hampering cell adhesion and regulating angiogenesis. 10,15 Indeed, increased levels of versican have been reported in different tumor types such as adenocarcinomas, [16][17][18] squamous cell carcinomas, 19,20 sarcomas, 21 mesotheliomas 22 and malignant melanomas. 23 In addition, versican expression has been associated with tumor progression and decreased survival in various tumor types.…”

Tissue-specificity of proteoglycans expression in different cancers

“…В целом в научной литературе имеются несколько работ по изучению паттернов экспрессии ПГ в различ-ных линиях опухолевых клеток in vitro и опухолей in vivo -в клетках рака яичника человека in vitro пока-зана экспрессия синдеканов-1, -2, -4, глипиканов-1, -3, -5 и CD44 [32]; в опухолевых клетках in vitro и опу-холях прямой кишки человека in vivo экспрессируют-ся синдекан-1, глипикан-1, перлекан, декорин, бигли-кан, версикан, аггрекан, серглицин, NG2, бревикан, люмикан и CD44 [27]; в опухолях плоскоклеточного рака гортани -аггрекан, версикан, декорин и бигли-кан [30]; в образцах нейроэндокринных опухолей че-ловека -глипиканы-1, -5 и синдекан-2 [29]; в злокаче-ственной мезотелиоме -синдеканы-1, -2, -4, бигликан и версикан [29]. Однако все эти исследования прово-дили с использованием различных методов и для раз-ного набора ПГ, в силу чего сопоставление данных в плане определения тканеспецифичности паттерна экспрессии ПГ является затруднительным.…”

“…Специфические наборы ПГ идентифицированы в опухолях молочной железы [25], предстательной железы [26], прямой кишки [27], гор-тани [28], плевры [29] и в образцах нейроэндокринных опухолей человека [30]. Вместе с тем косвенные данные указывают на возможность как типовой, так внутриопу-холевой гетерогенности экспрессии ПГ, и этот вопрос может быть тесно связан с морфологическими и функ-циональными характеристиками опухолевых клеток.…”