title: Neoplastic extracellular matrix environment promotes cancer invasion in vitro.
abstract: The invasion of carcinoma cells is a crucial feature in carcinogenesis. The penetration efficiency not only depends on the cancer cells, but also on the composition of the tumor microenvironment. Our group has developed a 3D invasion assay based on human uterine leiomyoma tissue. Here we tested whether human, porcine, mouse or rat hearts as well as porcine tongue tissues could be similarly used to study carcinoma cell invasion in vitro. Three invasive human oral tongue squamous cell carcinoma (HSC-3, SCC-25 and SCC-15), melanoma (G-361) and ductal breast adenocarcinoma (MDA-MB-231) cell lines, and co-cultures of HSC-3 and carcinoma-associated or normal oral fibroblasts were assayed. Myoma tissue, both native and lyophilized, promoted invasion and growth of the cancer cells. However, the healthy heart or tongue matrices were unable to induce the invasion of any type of cancer cells tested. Moreover, when studied in more detail, small molecular weight fragments derived from heart tissue rinsing media inhibited HSC-3 horizontal migration. Proteome analysis of myoma rinsing media, on the other hand, revealed migration enhancing factors. These results highlight the important role of matrix composition for cancer invasion studies in vitro and further demonstrate the unique properties of human myoma organotypic model.
authors.affiliation: Cancer and Translational Medicine Research Unit, University of Oulu, PO Box 5281, Aapistie 5A, FIN 90014 Oulu, Finland; Medical Research Center, Oulu University Hospital, Oulu, Finland. Electronic address: elias.sundquist@oulu.fi.
authors.forename: Elias
authors.initials: E
authors.lastname: Sundquist
authors.affiliation: Department of Pharmacology and Toxicology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Renko
authors.affiliation: Cancer and Translational Medicine Research Unit, University of Oulu, PO Box 5281, Aapistie 5A, FIN 90014 Oulu, Finland; Medical Research Center, Oulu University Hospital, Oulu, Finland; Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Salo
authors.affiliation: Department of Pharmacology and Toxicology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Magga
authors.affiliation: Department of Oral Diagnosis, Oral Pathology Division, Piracicaba Dental School, University of Campinas, Campinas, Brazil.
authors.forename: Nilva K
authors.initials: NK
authors.lastname: Cervigne
authors.affiliation: Cancer and Translational Medicine Research Unit, University of Oulu, PO Box 5281, Aapistie 5A, FIN 90014 Oulu, Finland; Medical Research Center, Oulu University Hospital, Oulu, Finland; Biobank Borealis of Northern Finland, Oulu University Hospital, Oulu, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Nyberg
authors.affiliation: Cancer and Translational Medicine Research Unit, University of Oulu, PO Box 5281, Aapistie 5A, FIN 90014 Oulu, Finland; Department of Clinical Chemistry, Institute of Diagnostics, University of Oulu, Oulu, Finland; Northern Laboratory Centre NordLab, Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
authors.affiliation: Biocenter Oulu, Oulu, Finland; Department of Pathology, Institute of Diagnostics, University of Oulu, Oulu, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Vuolteenaho
authors.affiliation: Mass Spectrometry Laboratory, Brazilian Biosciences National Laboratory-CNPEM, Campinas, Brazil.
authors.forename: Flávia
authors.initials: F
authors.lastname: Zandonadi
authors.affiliation: Mass Spectrometry Laboratory, Brazilian Biosciences National Laboratory-CNPEM, Campinas, Brazil.
authors.forename: Adriana F
authors.initials: AF
authors.lastname: Paes Leme
authors.affiliation: Department of Oral Diagnosis, Oral Pathology Division, Piracicaba Dental School, University of Campinas, Campinas, Brazil.
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Coletta
authors.affiliation: Department of Pharmacology and Toxicology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland; Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.affiliation: Cancer and Translational Medicine Research Unit, University of Oulu, PO Box 5281, Aapistie 5A, FIN 90014 Oulu, Finland; Medical Research Center, Oulu University Hospital, Oulu, Finland; Department of Oral and Maxillofacial Diseases, University of Helsinki, and HUSLAB, Helsinki, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000473:pathology; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005612:Freeze Drying; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000473:pathology; D009214:Myoma / Q000473:pathology; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D012995:Solubility; D034421:Sus scrofa; D014059:Tongue / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D011956:Receptors, Cell Surface; D003094:Collagen
keywords: Carcinoma; Extracellular matrix; Invasion; Myoma; Organotypic model; migration