title: The tumor microenvironment promotes cancer progression and cell migration.
abstract: The tumor microenvironment contributes to cancer progression, in part through interactions between tumor and normal stromal cells. This study analyzed morphological and molecular changes induced in co-cultured human fibroblasts (HFs) and the MG-63 osteosarcoma cell line. Co-cultured cell monolayers were morphologically analyzed using high resolution scanning electron microscopy (HR-SEM), and trans-well assays were performed to assess cell migration and invasion. Proteins involved in inflammatory responses, cancer cell invasion, and angiogenesis were assessed using western blotting. HR-SEM showed progressive spatial orientation loss by fibroblasts in contact with MG-63s, while MG-63s proliferated rapidly and invaded HF space. Trans-well assays showed enhanced MG-63 migration in the presence of HFs. IL-6 expression was increased in co-cultured HFs, possibly stimulated by TNF-α. HFs do not normally express YKL-40 but did so in co-culture. Band densitometric analyses showed that increasing YKL-40 expression was followed by VEGF overexpression, especially in MG-63s. Finally, our results confirmed fibroblasts as the main matrix metalloproteinase source in this tumor microenvironment. Our study sheds new light on how tumor-stroma interactions promote tumor development and progression, and may support identification of novel anti-cancer therapeutics.
authors.affiliation: DIBINEM, University of Bologna Department of Biomedical and Neuromotor Sciences, 40126 Bologna, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Salvatore
authors.affiliation: DIBINEM, University of Bologna Department of Biomedical and Neuromotor Sciences, 40126 Bologna, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Teti
authors.affiliation: DIBINEM, University of Bologna Department of Biomedical and Neuromotor Sciences, 40126 Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Focaroli
authors.affiliation: DIMEC, University of Bologna, Department of Medical and Surgical Sciences, 40126 Bologna, Italy.
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Mazzotti
authors.affiliation: Rizzoli Orthopaedhic Institute, 40136 Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mazzotti
authors.affiliation: DIBINEM, University of Bologna Department of Biomedical and Neuromotor Sciences, 40126 Bologna, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Falconi
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071451:Chitinase-3-Like Protein 1 / Q000378:metabolism; D018920:Coculture Techniques; D018450:Disease Progression; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D015398:Signal Transduction; D013997:Time Factors; D059016:Tumor Microenvironment; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases
keywords: co-culture; human fibroblasts; osteosarcoma; tumor microenvironment; tumor stroma