Web of Science: 5 citations, Scopus: 5 citations, Google Scholar: citations,
Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models
Álamo, Patricia (Institut d'Investigació Biomèdica Sant Pau)
Gallardo, Alberto (CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN))
Pavón Ribas, Miguel Ángel (Institut d'Investigació Biomèdica Sant Pau)
Casanova Rigat, Isolda (Institut d'Investigació Biomèdica Sant Pau)
Trias, Manuel (Institut d'Investigació Biomèdica Sant Pau)
Mangues, Maria Antonia (Institut d'Investigació Biomèdica Sant Pau)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Mangues, Ramon (Institut d'Investigació Biomèdica Sant Pau)
Céspedes, Maria Virtudes (Institut d'Investigació Biomèdica Sant Pau)

Date: 2014
Abstract: Mouse colorectal cancer (CRC) models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT). This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from nonmetastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT) group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC.
Note: Número d'acord de subvenció ISCIII/PI12/01861
Note: Número d'acord de subvenció AGAUR/2009-SGR1437
Note: Número d'acord de subvenció AGAUR/2009-FIB00457
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; altres ; publishedVersion
Subject: Collective invasion ; Colorectal cancer model ; Metastasis ; Orthotopic injection ; Single tumour cell ; Subcutaneous preconditioning
Published in: Disease Models and Mechanisms, Vol. 7, Núm. 3 (march 2014) , p. 387-396, ISSN 1754-8411

Adreça alternativa: http://dmm.biologists.org/content/7/3/387
DOI: 10.1242/dmm.013995
PMID: 24487410


13 p, 6.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Published articles

 Record created 2019-05-22, last modified 2019-12-09



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