Gene expression profiles in three histologic types, clear-cell, endometrioid and serous ovarian carcinomas.

Ovarian carcinoma is the most lethal type of gynecologic malignancy in the Western world. Majority of early stage ovarian cancers are asymptomatic and this is the main reason that more than two-thirds of patients are diagnosed with advanced disease. Ovarian tumors are heterogeneous and the different histologic subtypes are further classified as benign, borderline (low-grade) and malignant (high-grade) to reflect their behavior. The aim of the study was to analyze gene expression profiles in three histologic types of ovarian carcinoma in an attempt to find the molecular differences among serous, endometrioid and clear cell subtypes. The analysis of gene expression was performed on 57 samples of ovarian carcinoma. RNA was isolated from the ovarian cancer tissues. The gene expression changes were determined by microarray analysis and quantitative real time polymerase chain reaction (qRT-PCR). Measurement of relative gene expression levels was used to identify molecular differences among three histologic types of ovarian carcinoma (clear-cell, endometrioid and serous). Unsupervised statistical analysis revealed four biological subtypes among three histotypes under study. The endometrioid ovarian carcinoma was divided into two molecular subtypes. The biggest molecular differences were observed between clear-cell and serous carcinomas (1070 genes, FDR 0.05), the smallest between endometrioid and serous carcinomas (81 genes, FDR 0.05). The biggest group of differentially expressed genes was involved in transport and metabolism. This finding can explain the differences in the response to chemotherapy observed among different histologic types of ovarian carcinomas. In conclusion, we found TCF2 (HNF1B) gene as a suitable marker for ovarian clear cell carcinoma. Gene expression profiling also shed light on the molecular mechanisms of different chemoresistance among the analyzed histotypes.

The influence of neuropilin-1 silencing on semaphorin 3A and 3C activity in B16(F10) murine melanoma cells.

Neuropilin-1 (Nrp1), originally characterized as an adhesion molecule in the nervous system, is a co-receptor for class-3 semaphorins. Neuropilins and semaphorins are highly expressed in a wide spectrum of tumors and have been shown to influence their growth and vascularization. Despite the growing body of data on neuropilin/semaphorin regulation of tumor growth, still the exact mechanism of their activity remains to be elucidated. Previously published data suggests that Nrp1 has both anti- and promigratory characteristics in different tumor types, although no data is available on its role in melanoma cells. In this paper, we studied the effect of Nrp1 downregulation on B16(F10) melanoma cells migration. Our results show that the silencing of Nrp1 significantly increases the overall mobility of B16(F10) cells and changes their morphology. Moreover, Nrp1-silenced B16(F10) cells show a decreased response to Sema3A. We also observed reduced binding of Sema3A to these cells. Contrarily, no changes were observed in the binding of Sema3C to Nrp1-silenced B16(F10) cells, nor in its chemorepellent activity. Our results suggest that modulation of B16(F10) cells migratory ability by semaphorin 3A can be preferentially mediated by Nrp1, while the contribution of semaphorin 3C in this process is less evident. In addition, silencing of Nrp1 did not change the migratory ability of B16(F10) cells towards VEGF.