



@article {3270,
	title = {Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y 1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity},
	journal = {Oncogene},
	volume = {33},
	year = {2014},
	note = {Cited By (since 1996):2Export Date: 21 November 2014},
	month = {2014},
	pages = {2123 - 2133},
	abstract = {The interactions between cancer cells and their microenvironment are crucial for malignant progression, as they modulate invasion-related activities. Tumor-associated macrophages are generally considered allies in the process of tumor progression in several types of cancer, although their role on gastric and colorectal carcinomas is still poorly understood. In this report, we studied the influence of primary human macrophages on gastric and colorectal cancer cells, considering invasion, motility/migration, proteolysis and activated intracellular signaling pathways. We demonstrated that macrophages stimulate cancer cell invasion, motility and migration, and that these effects depend on matrix metalloproteinase (MMP) activity and on the activation of epidermal growth factor receptor (EGFR) (at the residue Y 1086), PLC-γ (phospholipase C-gamma) and Gab1 (GRB2-associated binding protein-1), as evidenced by siRNA (small interference RNA) experiments. Epidermal growth factor (EGF)-immunodepletion impaired macrophage-mediated cancer cell invasion and motility, suggesting that EGF is the pro-invasive and pro-motile factor produced by macrophages. Macrophages also induced gastric and colorectal cancer cell phosphorylation of Akt, c-Src and ERK1/2, and led to an increase of RhoA and Cdc42 activity. Interestingly, whereas macrophage-mediated cancer cell c-Src and ERK1/2 phosphorylation occurred downstream EGFR activation, Akt phosphorylation seems to be a parallel event, taking place in an EGFR-independent manner. The involvement of EGF, EGFR-downstream signaling partners and MMPs in macrophage-mediated invasion provides novel insights into the molecular crosstalk established between cancer cells and macrophages, opening new perspectives for the design of new and more efficient therapeutic strategies to counteract cancer cell invasion. {\textcopyright} 2014 Macmillan Publishers Limited.},
	keywords = {cancer cell invasion, colon cancer, Gastric cancer, invasion-related signaling pathways, Macrophages, tumor microenvironment},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899425243\&partnerID=40\&md5=beff5192ff42940c75fef8b48ebd3ae7},
	author = {Cardoso, A.P. and Pinto, M.L. and Pinto, A.T. and Oliveira, M.I. and Pinto, M.T. and Gon{\c c}alves, R. and Relvas, J.B. and Figueiredo, C. and Seruca, R. and Mantovani, A. and Mareel, M. and Barbosa, M.A. and Oliveira, M.J.}
}
@booklet {2867,
	title = {Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity},
	howpublished = {Oncogene},
	year = {2013},
	note = {Cited By (since 1996):1Export Date: 12 December 2013Source: ScopusArticle in Press},
	month = {2013///},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876908646\&partnerID=40\&md5=bcc2929bb93817db3dc0e3421c420722},
	author = {Cardoso, A.P. and Pinto, M.L. and Pinto, A.T. and Oliveira, M.I. and Pinto, M.T. and Gon{\c c}alves, R. and Relvas, J.B. and Figueiredo, C. and Seruca, R. and Mantovani, A. and Mareel, M. and Barbosa, M.A. and Oliveira, M.J.}
}
@article {2268,
	title = {Bioactivity of immobilized EGF on self-assembled monolayers: Optimization of the immobilization process},
	journal = {Journal of Biomedical Materials Research - Part AJ. Biomed. Mater. Res. Part A},
	volume = {94},
	year = {2010},
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},
	month = {2010///},
	pages = {576 - 585},
	abstract = {Last trends in Biomaterials focus the mimic of cellular environments capable to control cellular responses. Epidermal growth factor (EGF) is a pleiotropic cytokine known to regulate cell proliferation, differentiation, and death. This study aims to optimize the immobilization of EGF on 11-mercapto-1-undecyl-tetra(ethylene)glycol (EG4) - self-assembled monolayers (SAMs) and to establish a new model surface to study EGF-mediated signaling. Gold substrates were modified with a monolayer of EG4 and N,N'- carbonyldiimidazole (CDI) was used to activate hydroxyl terminated groups of EG4-SAMs. EGF was then immobilized on activated EG4-SAMs at pH 7.4, 4{\textdegree}C, and 100 rpm. Different immobilization reaction times were tested as well as different CDI concentrations to optimize the reaction conditions and obtain a range of immobilized EGF concentrations on the surfaces. Surface characterization of EGF-SAMs was performed using radiolabeling, water contact angle measurements, X-ray photoelectron spectroscopy, and ELISA. Phosphorylation of EGFR on BT-20 breast cancer cell line by EGF-SAMs was tested by immunostaining. EGF was successfully immobilized on EG4-SAMs, at 4{\textdegree}C and pH 7.4 in a range of concentrations from 3.6 {\textpm} 0.8 to 17.6 {\textpm} 1.5 ng/cm                        2. The concentration of EGF increases with immobilization time and with the CDI concentration reaching the maximum for surfaces activated with 30 mg/mL of CDI after 48 h. The bioactivity of EGF-SAMs was confirmed by immunostaining of phospho-EGFR of BT-20 cells. This study described EGF immobilization on EG4-SAMs at different concentrations, which could be important surface models to study specific protein interactions at the molecular level evolving EGF-family of proteins. {\textcopyright} 2010 Wiley Periodicals, Inc. J.
},
	keywords = {Adsorption, Angle measurement, article, Biocompatible Materials, Biological materials, Breast cancer cells, cancer cell culture, Carbonyldiimidazole, Cell culture, Cell immobilization, Cell Line, Tumor, cell proliferation, Cellular environment, Cellular response, Concentration (process), Concentration of, Contact angle, controlled study, Cytokines, EGF, Electron energy levels, enzyme linked immunosorbent assay, Enzyme-Linked Immunosorbent Assay, epidermal growth factor, Epidermal growth factors, Ethylene, Glycols, gold, Gold substrates, human, human cell, Humans, Hydroxyl-terminated, Imidazoles, Immobilization process, Immobilization reaction, immunofluorescence, immunohistochemistry, Immunostaining, Molecular levels, Nanostructured materials, Nanostructured surface, Nanostructured surfaces, New model, Optimization, Phosphorylation, Photoelectron spectroscopy, Polyethylene Glycols, Protein adsorption, protein immobilization, protein interaction, protein phosphorylation, Proteins, Radiolabeling, Radioligand Assay, Reaction conditions, reaction optimization, Receptor, Epidermal Growth Factor, Sams, self assembled monolayer, Self assembled monolayers, Self-assembled monolayers, Sulfhydryl Compounds, Surface characterization, Surface functionalization, Surface models, Surface Properties, Water contact angle measurement, X ray photoelectron spectroscopy},
	isbn = {15493296 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77953815323\&partnerID=40\&md5=7b54d717bbba475933dd86cc62659acc},
	author = {Gon{\c c}alves, R. and Martins, M.C.L. and Oliveira, M.J. and Almeida-Porada, G. and Barbosa, M.A.}
}
@article {2286,
	title = {Dynamic cell-cell interactions between cord blood haematopoietic progenitors and the cellular niche are essential for the expansion of CD34                    +, CD34
                    +CD38
},
	journal = {Journal of Tissue Engineering and Regenerative MedicineJ. Tissue Eng. Regenerative Med.},
	volume = {4},
	year = {2010},
	note = {Cited By (since 1996): 8Export Date: 21 November 2012Source: Scopusdoi: 10.1002/term.226PubMed ID: 19937912Language of Original Document: EnglishCorrespondence Address: Da Silva, C. L.; IBB-Institute for Biotechnology and Bioengineering, Centre for Biological and Chemical Engineering, Instituto Superior T{\'e}cnico, Avenida Rovisco Pais, 1049-001 Lisbon, Portugal; email: claudialobato@ist.utl.ptChemicals/CAS: Antigens, CD34; Antigens, CD38, 3.2.2.5; Antigens, CD7; SuspensionsReferences: Alakel, N., Jing, D., Muller, K., Direct contact with mesenchymal stromal cells affects migratory behavior and gene expression profile of CD133 + hematopoietic stem cells during ex vivo expansion (2009) Exp Hematol, 37 (4), pp. 504-513;Almeida-Porada, G., Brown, R.L., MacKintosh, F.R., Evaluation of serum-free culture conditions able to support the ex vivo expansion and engraftment of human hematopoietic stem cells in the human-to-sheep xenograft model (2000) J Hematother Stem Cell Res, 9 (5), pp. 683-693; 
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},
	month = {2010///},
	pages = {149 - 158},
	abstract = {Most clinical applications of haematopoietic stem/progenitor cells (HSCs) would benefit from their ex vivo expansion to obtain a therapeutically significant amount of cells from the available donor samples. We studied the impact of cellular interactions between umbilical cord blood (UCB) haematopoietic cells and bone marrow (BM)-derived mesenchymal stem cells (MSCs) on the ex vivo expansion and differentiative potential of UCB CD34                        +-enriched cells. UCB cells were cultured: (a) directly in contact with BM MSC-derived stromal layers (contact); (b) separated by a microporous membrane (non-contact); or (c) without stroma (no stroma). Highly dynamic culture events occurred in HSC-MSC co-cultures, involving cell-cell interactions, which preceded HSC expansion. Throughout the time in culture [18 days], total cell expansion was significantly higher in contact (fold increase of 280 {\textpm} 37 at day 18) compared to non-contact (85 {\textpm} 25). No significant cell expansion was observed in stroma-free cultures. CD34 
                        + cell expansion was also clearly favoured by direct contact with BM MSCs (35 {\textpm} 5- and 7 {\textpm} 3-fold increases at day 18 for contact and non-contact, respectively). Moreover, a higher percentage of CD34 
                        +CD38
},
	keywords = {Antigens, CD34, Antigens, CD38, Antigens, CD7, article, Bone marrow microenvironment, CD34 antigen, CD38 antigen, CD7 antigen, cell adhesion, Cell Communication, cell contact, Cell culture, cell differentiation, cell interaction, cell proliferation, Cells, Cultured, cellular distribution, clonogenic assay, coculture, Coculture Techniques, Colony-Forming Units Assay, controlled study, Ex vivo expansion, ex vivo study, Fetal Blood, flow cytometry, Haematopoietic stem/progenitor cells, hematopoietic stem cell, Hematopoietic Stem Cells, human, human cell, Humans, Lymphocytes, lymphoid cell, Mesenchymal stem cell, Mesenchymal Stem Cells, Microscopy, Electron, Scanning, phenotype, priority journal, Scanning electron microscopy, somatic gene therapy, stem cell expansion, Stem Cell Niche, stroma cell, Suspensions, umbilical cord blood},
	isbn = {19326254 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77649221153\&partnerID=40\&md5=822edb72ad71976fb309b0e658137bc5},
	author = {Da Silva, C.L. and Gon{\c c}alves, R. and Dos Santos, F. and Andrade, P.Z. and Almeida-Porada, G. and Cabral, J.M.S.}
}
