Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: A novel character of tumor educated fibroblasts

  • Authors: Genichiro Ishii, Hiroko Hashimoto, Kiyoshi Asada, Takashi Ito, Ayuko Hoshino, Satoshi Fujii, Motohiro Kojima, Takeshi Kuwata, Kenichi Harigaya, Kanji Nagai, Toshikazu Ushijima, Atsushi Ochiai
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  • Published online on: Sunday, August 1, 2010
  • Pages: 317-325
  • DOI: 10.3892/ijo_00000680

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.
Journal Cover

August 2010
Volume 37 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
(total number of cites)

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APA
Ishii, G., Hashimoto, H., Asada, K., Ito, T., Hoshino, A., Fujii, S., Kojima, M., Kuwata, T., Harigaya, K., Nagai, K., Ushijima, T., & Ochiai, A. (2010). Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: A novel character of tumor educated fibroblasts. International Journal of Oncology, 37(2), 317-325.
MLA
Ishii, Hashimoto, Asada, Ito, Hoshino, Fujii, Kojima, Kuwata, Harigaya, Nagai, Ushijima, and Atsushi Ochiai. "Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: A novel character of tumor educated fibroblasts." International Journal of Oncology International Journal of Oncology 37.2 (2010): 317-325.
Chicago
Ishii, Hashimoto, Asada, Ito, Hoshino, Fujii, Kojima, Kuwata, Harigaya, Nagai, Ushijima, and Atsushi Ochiai. "Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: A novel character of tumor educated fibroblasts." International Journal of Oncology International Journal of Oncology 37 no. 2 (2010): 317-325.