Activated leukocyte cell adhesion molecule expression and shedding in thyroid tumors
Authors: Marco A Pierotti
Luca Da Riva
Silvano Ferrini
Silvana Canevari
Italia Bongarzone
Piera Mondellini
Marina Fabbi
Francesca Miccichè
Silvana Pilotti
Journal: PLoS ONE (2011)
Discipline: Multidisciplinary
Keywords: ALCAM; cancer; thyroid tumors; cell adhesion; shedding
Affiliations: Proteomics Laboratory, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Abstract:  Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology. 

Retracted: No

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 Via https: www.ilfattoquotidiano.it in-edicola articoli 2019 11 28 ricerche-mediche-aggiustate-pero-la-scienza-tace 5583974 (and Google translate) Fixed medical research, but science is silent by Gianni Barbacetto | NOVEMBER 28, 2019 u201cFor justice everything is fine. But is this okay for the scientific community ? Is it possible to falsify the images of the experiments, or avoid doing the control experiment, without anyone having anything to say? These are the questions that remain, at the end of a long judicial investigation by the Milan Public Prosecutor s Office on some articles of the most important Italian scientists engaged in cancer research. Professor Alberto Mantovani of Humanitas, Pier Giuseppe Pelicci of Ieo, Pier Paolo Di Fiore of Ifom, Marco Pierotti, with Maria Angela Greco, Elena Tamburini and Silvana Pilotti of the Cancer Institute, were investigated by prosecutors Francesco Cajani and Paolo Filippini for having manipulated the images of some of their studies published in international scientific journals. They are research luminaries who maneuver millions of euros from public funds, private donations, 5 per thousand collections . They received, only in the period analyzed by the Public Prosecutor (2005-2012), very high figures: 9.37 million Di Fiore; 3.06 Mantovani; 1.48 Pelicci; 3.60 Pierotti, for a total of 17 million paid by the CNR , the Ministry of Health and the University. And they got caught  fixing their research records. Now the judge of the preliminary investigation Sofia Fioretta has closed the investigation started in 2014, dismissing the accusations and arguing - with bold arguments - that the professors  did not carry out any falsification activities  . The two prosecutors had already requested the filing, arguing that the manipulations are established, but that the crime of  scientific fraud does not exist in Italy (as there is instead that of insurance fraud and sports fraud), therefore it is not possible pursue the behaviors of the seven excellent oncologists. The investigating judge was more creative : he recognized  a harmless and innocent fake , realized  because there was no time or money to perform the replication, or because competitors were coming first (what stupid scientists who do everything right instead ). Therefore,  insignificant errors were made . Replicas of the experiments were not carried out, but this  did not affect the content of the research and  did not undermine the scientific validity of the published thesis . In short: the luminaries were wrong, but in modest quantity . Yet the examinations of the experts of the Public Prosecutor s Office have ascertained the manipulations: three in the works of Pelicci-Ieo, four in those of the group of Pierotti-Istituto dei tumori (i.e. two by Pilotti and one by Greco and Tamburini), one in the works by Di Fiore-Ifom and one by Mantovani-Humanitas. But nothing wrong with that, that s okay, the investigating judge Fioretta reassures us. Closed the judicial game, at this point we ask some questions to the scientific community: 1. Are there, in scientific practice,  harmless and innocent false manipulations , but  of little significance ? 2. Is it normal that seven luminaries of oncology research publish images in international scientific journals that are manipulated in 21 out of 27 cases analyzed? 3. Is it compatible with the scientific method that, having performed the first experiment, one tarot the replica,  because there was no time or money to perform it,  or because competitors were arriving first ? 4. Since it is impossible, on the judicial level, to establish the direct connection between research carried out and funds obtained, is it still normal, on the scientific and ethical level, to obtain money, public and private, with the prestige gained (also) with fake research? 5. Is the scientific community sure that squaring up (corporately) and rejoicing in the  false innocents is the best way to defend science and the scientific method, now threatened by charlatans, scoundrels and no-vaxes?u201d ,