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Database of metastasis patterns in mouse models induced by injection of human cancer cell lines |
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RATIONALE Despite the recent discoveries, the biological and molecular understanding of the formation and localization of metastases is not fully known yet. In order to study the tumor evolution, the research mostly uses murine models. A common type of experiment involves the inoculation, by various techniques, of human tumor cell lines in immunosuppressed mouse models to avoid rejection reactions. In particular, this experimental model allows the evaluation of the effectiveness of potential anticancer therapies in vivo. By hand-curated literature screening we collected, in MetaTropismDB database, experimentally assessed data about the organotropism of several human cancer cell lines. In the reviewed studies, human cell lines have been injected in murine models in order to assess the patterns of metastasis. In particular, we collected all the experimental conditions and the obtained results, including the organs NOT affected by metastases. Currently, it stores the results of 474 experiments in which cell line injection in mouse models have been carried out. The database allows to easily highlight cell lines or particular clones with metastatic activity with similar organotropism, or alternatively, cell lines and clones which, although deriving from the same type of primary tumor, have tropism for different organs. This allows researchers to choose, with greater awareness and accuracy, the cell lines to be analyzed at the molecular level in order to investigate the biological bases of metastasis organotropism. CONTENT DESCRIPTION: MetaTropismDB Identifier This is an unique identifier assigned to each MetaTropismDB record. Cell line name We reported the cell line injected into mice in order to assess the metastatic patterns. We also reported the organ from which the cell line derives. Parental cell line Name of the cell line from which the injected cell line derives, according to Cellosaurus DB (https://web.expasy.org/cellosaurus/) or to the literature. Links to cell line DBs When available, links to cell line databases such as, Cellosaurus (https://web.expasy.org/cellosaurus/) and DMSZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen, www.dsmz.de), are reported. We also reported links to other databases, such as Cell Model Passports (https://cellmodelpassports.sanger.ac.uk) and CellFinder (www.cellfinder.org). Mouse model Mouse model used in the experiment is shown. Indeed, mouse models are necessary in cancer research. Numerous types of mice are manipulated to investigate the factors involved in malignant transformation, invasion and metastasis, as well as to examine the response to therapy. Murine models are subjected to xenotransplantation experiments of human cancer cell lines and, in order to avoid rejection reactions, they are severely immunocompromised. The most common mouse model is BALB/c athymic nude mice. Other immunocompromised mice are the athymic nude, C.B-17 SCID beige, C57BL/6, MF1, NIH-III nude, NMRI nude, NOD SCID gamma (NSG), NOD SCID, NOG and Swiss athymic nude mice. Links to mouse model laboratories When available, links to laboratories and services for mouse models are reported. They include The Jackson Laboratory (JAX, www.jax.org), Charles River Laboratories (www.criver.com/), ENVIGO (www.envigo.com), JANVIER LABS (https://janvier-labs.com), and TACONIC Biosciences (www.taconic.com). We also reported links to other databases, such as Mouse Genome Informatics, MGI (www.informatics.jax.org) and Mouse Phenome Database, MPD (https://phenome.jax.org). Injection method Inoculation method of tumour cell line into mice is shown. They can include: orthotopic injection (into the organ from which the cell line derives), subcutaneous injection, intracardiac injection, tail vein injection. Cell concentration Concentration of cells inoculated into mice, along with the used cell culture medium. Visualization methods Methods by which metastases were identified and localized. They can include: Autopsy, Histological examination, Immunohistochemistry, Bioluminescence, Fluorescence, Radiography. Induced primary tumour Site of primary tumour induced by cell line injection Rate of tumour induction This is the tumour take rate, expressed in percentage out of the number of tested mice. Tumour development time Timespan between injection and tumour onset. It ranges from some days to some weeks, and rarely months. Overall survival Timespan between injection and mouse death. Often, it is reported the time of autopsy. It ranges from some days to some weeks. Metastatic site Organ in which the metastasis developed. User can search for a specific organ with metastases. Not metastatic site Organ in which the metastasis did not develop. User can search for a specific organ without metastases. Metastasis development time Timespan between injection and metastasis formation. It ranges from some days to some weeks, and rarely months. Involved Genes We list the genes involved in the metastatic organotropism, as reported by Authors of the paper. The association between a gene and a specific tropism is generally identified by assessing its expression by microarray, qPCR or Western Blot in a organ-specific metastatic cell line. We also reported genes able to increase the metastatic potential, although not associated with the organotropism: these cases are clearly highlighted to the user. Fitting to clinical data For each experiment in mice, we assigned a fitting degree to clinical data of observed metastasis in human. The frequencies regarding sites of metastasis are reported in 1) Riihimaki et al. Clinical landscape of cancer metastases. Cancer Med. 2018; 7(11):5534-5542. PMID:30328287; 2) Bacci et al. Pattern of relapse in patients with osteosarcoma of the extremities treated with neoadjuvant chemotherapy. Eur J Cancer. 2001; 37(1):32-8. PMID:11165127; 3) Wang et al. Multi-organ distant metastases confer worse disease-specific survival in differentiated thyroid cancer. Thyroid. 2014; 24(11):1594-9. PMID:25162180. We assigned "0 (no fit)" to experiments where no metastasis is observed in mice. We assign "3 (high)" when the metastasis site observed in mice corresponds to the most frequent metastatic site in human. In addition, "1 (low)" and "2 (medium)" mean that metastasis site(s) observed in mice correspond(s) to only one or several human metastatic site(s), respectively. Note Here we reported some experimental details. For example, we indicated the specific bone name affected by metastasis, since in the main table, we simply reported "bone". Moreover, we described how some mice have been humanized by human tissue implants. We also pointed out the metastatic organs when neither the occurrence nor the frequency are reported in the paper. References Here we report the PubMed Identifier of the reference paper the experiment was derived from. HOW TO INTERPRET THE IMAGES The image depicted at the end of the result page shows the effects, in terms of metastasis frequency in each organ, deriving from different experimental conditions and stimuli (so collected in different database records) but belonging to the same paper (PubMed ID is shown). The results are reported through a yellow/black colour scale: yellow means low frequency of metastases (if completely absent, an 0 is added) and black means 100% of mice with metastases. The user can also select the database record from those present in the image. HOW TO CITE US MetaTropismDB: a database of organ-specific metastasis induced by human cancer cell lines in mouse models M Giulietti, M Bastianoni, M Cecati, A Ruzzo, M Bracci, M Malavolta, F Piacenza, R Giacconi, F Piva Database, Volume 2020, 2020, baaa100 DOI: 10.1093/database/baaa100 PMID: 33238004 |
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Computational Biology Group Polytechnic University of Marche, Italy | 2020 |
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