Tetraspanins are integral membrane proteins that associate with motility-related molecules such as integrins. Experimental studies have indicated that they may be important regulators of tumor invasion and metastasis, and high expression of the tetraspanin CD151 has been linked to poor prognosis in a number of cancers. Here, we show for the first time that genetic ablation of CD151 inhibits spontaneous metastasis in a transgenic mouse model of de novo tumorigenesis. To evaluate the effects of CD151 on de novo prostate cancer initiation and metastasis, a Cd151 À/À (KO) murine model was crossed with the Transgenic Adenocarcinoma of MouseProstate (TRAMP) model. Mice were analyzed for initiation of prostate tumor by palpation and primary tumors were analyzed by immunohistochemistry. Liver and lungs were examined for incidence and size of spontaneous metastatic lesions by histopathology. Knocking-out Cd151 had no significant effect on prostate cancer initiation or on expression of markers of proliferation, apoptosis, or angiogenesis in primary tumors. However, it did significantly decrease metastasis in a site-specific fashion, notably to the lungs but not the liver. Thus, CD151 acts principally as promoter of metastasis in this model. Prostate cancer is the second highest cause of cancerrelated deaths in men in most Western countries, with the majority of deaths attributed to late-stage metastatic disease. CD151 may prove to be a valuable prognostic marker for treatment stratification and is a possible antimetastatic target. Mol Cancer Res; 11(1); 95-105. Ó2012 AACR.

Prostate cancer is an extremely heterogeneous disease; patients that do progress to late-stage metastatic prostate cancer have limited treatment options, mostly palliative. Molecules involved in the metastatic cascade may prove beneficial in stratifying patients to assign appropriate treatment modalities and may also prove to be therapeutic antimetastatic targets. The tetraspanin group of molecules are integral membrane proteins that associate with motility-related proteins such as integrins. Clinical studies have mostly shown that reduced expression levels of the tetraspanin CD9 are correlated with tumour progression in a range of cancers. Furthermore, functional studies have shown CD9 to be involved in cell motility and adhesion and that it may influence metastasis. The effects of endogenous CD9 on prostate cancer initiation and progression were analysed by crossing a Cd9 2/2(KO) murine model with a model of de novo developing and spontaneously metastasising prostate cancer, namely the transgenic adenocarcinoma of mouse prostate model. Our study demonstrates for the first time that ablation of Cd9 had no detectable effect on de novo primary tumour onset, but did significantly increase metastasis to the liver but not the lungs.Prostate cancer is a very heterogeneous disease that in some patients will remain indolent while in others it will progress to incurable metastatic disease.1 At diagnosis, treatment options range from "watchful waiting" to radical prostatectomy with its associated deleterious effects. There are currently limited reliable prognostic indicators to guide patient stratification and choice of the most appropriate therapy. Altered regulation of various genes is associated with the metastatic cascade 2 and understanding these molecules may prove useful as potential prognostic markers and also provide new therapeutic targets.Tetraspanin proteins are classified by their topology and conserved sequence motifs. Notably, they consist of four transmembrane domains, two extracellular loops, one intracellular loop and amino-and carboxy-terminal intracellular tails. Tetraspanins function through association with other tetraspanins and also other membrane-bound proteins such as integrins, growth factors and signalling molecules to form tetraspanin-enriched microdomains (TEMs), reviewed in Ref. 3. They play regulatory roles in cellular functions essential for cancer progression such as cell signalling, adhesion and motility, reviewed in Refs. 4 and 5.The tetraspanin CD9 is widely expressed in human tissues and on many cell types including platelets and vascular endothelial cells.6 It is also known as motility-related protein 1 (MRP-1) and is located on human chromosome 12p13. One study that found an inverse correlation of CD9 expression with progressive cervical cancer also reported strong CD9 expression within specific regions of tumour invasion into lymphovascular spaces. 23 This suggests that CD9 may differentially affect particular aspects of tumour growth and progression. In contrast to the majority o...

In the 2010 book The Facebook Effect by David Kirkpatrick, Facebook founder Mark Zuckerberg made the claim that ‘users have one identity’. Through a critical theoretical analysis of a series of case studies of people being outed by Facebook, this article argues that ‘one identity’ and Facebook’s use of algorithms to drive profits are fundamentally incongruous with prevailing intersectional scholarship. The case studies articulate a theoretical framework that ties intersectional conceptions of gender and sexuality to social media and privacy. By aligning intersectional and privacy theories, the article argues that ‘one identity’ constitutes a violation of privacy norms as conceptualized by Helen Nissenbaum’s framework of contextual integrity. The article concludes that Facebook is anathema to the privacy and real life experiences of its users, which cannot fit into static categories and which change over time, mitigating the potential for the performance of fluid and intersectional identities.

<p>PDF file - 60K, Breeding strategy to produce the experimental animals. To produce the required F1 experimental animals, heterozygous TRAMP C57BL/6 females were crossed with Cd151 KO C57BL/6 males. The resultant Cd151 heterozygous C57BL/6 and TRAMP heterozygous females were then crossed with Cd151 heterozygous FVB/N males. Genetic frequencies shown are specific for the male experimental animals. This breeding program ensured the absence of kidney disease that occurs in FVB/N Cd151 homozygous KO mice. It also ensured a homogeneous genetic background for test and control mice which, in addition, were littermates</p>

<p>PDF file - 112K, Characterisation for expression of the epithelial cell marker cell marker, E-Cadherin. 5 �m FFPE sections of normal prostate glands from 20 week old TRAMP negative animals along with sections from poorly differentiated primary prostate tumours from TRAMP positive animals were characterised by indirect peroxidase IHC with the anti E-Cadherin antibody (clone 36) that labels epithelial cells, as the primary antibody. The epithelial cells in the normal prostate glands in Panel A stained highly and specifically for E-Cadherin both on the membrane and also through the cytoplasm. In Panel B, the prostate gland that displays PIN has reduced labelling of E-cadherin and the surrounding poorly differentiated prostate tumour tissue was void of specific labelling for E-cadherin</p>