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Malignant Epithelial Cells (malignant + epithelial_cell)
Selected AbstractsDecrease in stromal androgen receptor associates with androgen-independent disease and promotes prostate cancer cell proliferation and invasionJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2008Yirong Li Abstract Androgen receptor (AR) is expressed in both stromal and epithelial cells of the prostate. The majority of studies on AR expression and function in prostate cancer is focused on malignant epithelial cells rather than stromal cells. In this study, we examined the levels of stromal AR in androgen-dependent and -independent prostate cancer and the function of stromal AR in prostate cancer growth and invasion. We showed that stromal AR levels were decreased in the areas surrounding cancerous tissue, especially in androgen-independent cancer. Using two telomerase-immortalized human stromal cell lines, one AR-positive and the other AR-negative, we demonstrated that stromal cells lacking AR stimulated cell proliferation of co-cultured prostate cancer cells in vitro and enhanced tumour growth in vivo when co-injected with PC3 epithelial cells in nude mice. In contrast, stromal cells expressing AR suppressed prostate cancer growth in vitro and in vivo. In parallel with cancer growth, in vitro invasion assays revealed that stromal cells lacking AR increased the invasion ability of PC3 cell by one order of magnitude, while stromal cells expressing AR reduced this effect. These results indicate a negative regulation of prostate cancer growth and invasion by stromal AR. This provides potentially new mechanistic insights into the failure of androgen ablation therapy, and the reactivation of stromal AR could be a novel therapeutic approach for treating hormone refractory prostate cancer. [source] Stromelysin-3 suppresses tumor cell apoptosis in a murine model,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2001Erxi Wu Abstract Stromelysin-3 (STR-3) is a matrix metalloproteinase with a unique pattern of expression and substrate specificity. During embryogenesis and remodeling of normal adult tissues, STR-3 is produced by stromal cells in direct contact with epithelial cells undergoing regional apoptosis and selective cell survival. STR-3 is also overexpressed by interdigitating stromal cells in primary epithelial malignancies. Although STR-3 does not degrade classic extracellular matrix components, the enzyme promotes the establishment of local tumors in nude mice by as yet undefined mechanisms. STR-3 is induced when malignant epithelial cells come into contact with surrounding stromal elements; the active stromal cell-derived 45 kDa enzyme is subsequently processed to a 35 kDa protein without enzymatic activity. We have generated MCF-7 transfectants expressing wild type or catalytically inactive 45 kDa STR-3 (STR-3wt and STR-3cat- ) or secreted 35 kDa STR-3 (35 kDa STR-3sec) and evaluated their implantation and survival in nude mice. Tumors developed significantly more rapidly in animals receiving STR-3wt, rather than vector-only, STR-3cat- or 35 kDa STR-3sec transfectants. Most importantly, STR-3wt tumors had a significantly lower percentage of apoptotic cells than tumors derived from vector-only, STR-3cat- or 35 kDa STR-3sec transfectants. Taken together, these studies suggest that the active STR-3 enzyme may increase tumor take by suppressing tumor cell apoptosis and that 45 kDa to 35 kDa STR-3 processing limits STR-3 activity at the tumor/stromal interface. Because STR-3 is secreted as an active enzyme rather than a proform, subsequent 45 kDa to 35 kDa STR-3 processing may represent a novel mechanism for regulating enzymatic activity. J. Cell. Biochem. 82: 549,555, 2001. © 2001 Wiley-Liss, Inc. [source] Double immunostaining with p63 and high-molecular-weight cytokeratins distinguishes borderline papillary lesions of the breastPATHOLOGY INTERNATIONAL, Issue 3 2007Shu Ichihara Papillary breast lesions remain a source of diagnostic confusion because the full range of epithelial proliferations may arise within, or secondarily involve, papilloma. The expression of p63 and high-molecular-weight cytokeratins (HMWCK) was studied simultaneously in 33 papillary lesions including intraductal papilloma (IP, n = 10), atypical papilloma (AP, n = 8) and intraductal papillary carcinoma (IPC, n = 15) by double immunostaining. The myoepithelial cell nuclei were stained dark brown whereas the cytoplasms of usual ductal hyperplasia (UDH) and myoepithelium were stained purple. The myoepithelial layer was recognized as a dark brown dotted line at the epithelial stromal junction in all IP (10/10), most AP (7/8) and some IPC (7/15), suggesting that the retained myoepithelial layer in the papillary processes does not necessarily guarantee benignity. However, the malignant epithelial cells in AP and IPC were typically recognized as monotonous populations unstained with either chromogen. These monotonous cells contrasted with the proliferating cells of UDH in papilloma, which had intense purple cytoplasm in a mosaic-like fashion. The present data suggest that the double immunostaining with the two popular antibodies p63 and HMWCK is a useful tool for reproducible classification of papillary breast lesions. [source] Selective over-expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2007K Sahadevan Abstract Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway. To identify the most relevant targets, we simultaneously investigated FGFR1,4 expression using a prostate cancer tissue microarray (TMA) and in laser capture microdissected (LCM) prostate epithelial cells. In malignant prostates (n = 138) we observed significant FGFR1 and FGFR4 protein over-expression in comparison with benign prostates (n = 58; p < 0.0001). FGFR1 was expressed at high levels in the majority of tumours (69% of grade 3 or less, 74% of grade 4 and 70% of grade 5), while FGFR4 was strongly expressed in 83% of grade 5 cancers but in only 25% of grade 1,3 cancers (p < 0.0001). At the transcript level we observed a similar pattern, with FGFR1 and FGFR4 mRNA over-expressed in malignant epithelial cells compared to benign cells (p < 0.0005 and p < 0.05, respectively). While total FGFR2 was increased in some cancers, there was no association between expression and tumour grade or stage. Transcript analysis, however, revealed a switch in the predominant isoform expressed from FGFR2IIIb to FGFR2IIIc among malignant epithelial cells. In contrast, protein and transcript expression of FGFR3 was very similar between benign and cancer biopsies. The functional effect of targeting FGFR4 in prostate cancer cells has not previously been investigated. In in vitro experiments, suppression of FGFR4 by RNA interference effectively blocked prostate cancer cell proliferation (p < 0.0001) and invasion (p < 0.001) in response to exogenous stimulation. This effect was evident regardless of whether the cells expressed the FGFR4 Arg388 or Gly388 allele. In parallel experiments, FGFR3 suppression had no discernible effect on cancer cell behaviour. These results suggest evidence of selective over-expression of FGFR1 and FGFR4 in clinical prostate cancer and support the notion of targeted inhibition of these receptors to disrupt FGF signalling. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | ||||||||||