Subcutaneous preconditioning increases invasion and metastatic dissemination in mouse colorectal cancer models
| Autor: | Álamo, Patricia, Gallardo, Alberto, Pavón Ribas, Miguel Ángel, Casanova Rigat, Isolda, Trias, Manuel, Mangues, Ma Antonia, Vázquez Gómez, Esther, Villaverde Corrales, Antonio, Mangues, Ramon, Céspedes, María Virtudes, Universitat Autònoma de Barcelona |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Colorectal cancer
Cell Survival Neuroscience (miscellaneous) Medicine (miscellaneous) lcsh:Medicine Apoptosis Cell Count Colorectal cancer model General Biochemistry Genetics and Molecular Biology Collective invasion Metastasis Orthotopic injection Mice Subcutaneous Tissue Immunology and Microbiology (miscellaneous) Peritoneum Cell Line Tumor medicine lcsh:Pathology Animals Humans Single tumour cell Neoplasm Invasiveness Resource Article Cell Aggregation Cell Proliferation Subcutaneous preconditioning business.industry lcsh:R medicine.disease Xenograft Model Antitumor Assays Cell aggregation digestive system diseases Neoplasm Proteins medicine.anatomical_structure Lymphatic system Lymphatic Metastasis Immunology Cancer research Lymph Lymph Nodes business Colorectal Neoplasms Subcutaneous tissue lcsh:RB1-214 |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 7, Iss 3, Pp 387-396 (2014) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | MMouse colorectal cancer (CRC) models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, hematological and transceolomic 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 and SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT). This subcutaneous preconditioning significantly enhanced metastasic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung and liver, whereas in the SW48 model it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumor in the SC+ORT group was significantly reduced compared to the direct orthotopic injection (ORT group). Moreover, in HCT116 tumors the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumor model, we observed a trend towards a higher number of tumor 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 tumor cell survival and invasion at the tumor invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate antimetastatic drugs against CRC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|