title: Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: a novel character of tumor educated fibroblasts.
abstract: It is now clear that the association between cancer cells and recruited fibroblasts (cancer-associated fibroblasts; CAFs) leads to alteration of the biological properties of both types of cells and creates a specific microenvironment. Here we report a novel biological property of CAFs and its cellular mechanism using in vivo and in vitro model. Cultured CAFs derived from human lung cancer tissue displayed significantly higher migration activity in response to PDGF-BB than that of fibroblasts from corresponding non-cancerous tissue (NCAFs). Moreover, KM104GFP (GFP-labeled human fibroblast cell line) co-cultured with human cancer cell line Capan-1 showed significantly higher migration activity than KM104GFP alone. No such phenomenon occurred when KM104GFP and Capan-1 were cultured separately. Even after KM104GFP were sorted from co-cultured Capan-1, KM104GFP retained their enhanced migration activity until passage-5 of culture in the absence of cancer cells. Despite a similar level of phosphorylation of ERK1/2 after exposure to PDGF-BB, the inhibitory effect of MEK inhibitor was significantly higher on migration of KM104GFP that had been sorted from co-cultured Capan-1 than of KM104GFP alone. This higher dependence on ERK1/2 signaling for cell migration was also seen in CAFs obtained from cancer tissue. The results of this study indicate that by association with cancer cells, CAFs can acquire enhanced migration activity which could be kept after separation from cancer cells and suggest the possibility that higher dependence on ERK1/2 signaling for enhanced migration activity would be one of the biological properties of CAFs.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, Kashiwa, Chiba 277-8577, Japan. gishii@east.ncc.go.jp
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asada
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Ayuko
authors.initials: A
authors.lastname: Hoshino
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuwata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harigaya
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology* / Q000502:physiology / Q000637:transplantation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D015398:Signal Transduction / Q000502:physiology; D014183:Transplantation, Heterologous
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin