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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2000 Dec;91(12):1285–1295. doi: 10.1111/j.1349-7006.2000.tb00916.x

In vivo and in vitro Interactions between Human Colon Carcinoma Cells and Hepatic Stellate Cells

Sadatoshi Shimizu 1, Nobuya Yamada 1,✉, Tetsuji Sawada 1, Kazuo Ikeda 2, Norifumi Kawada 3, Syuichi Seki 3, Kenji Kaneda 2, Kosei Hirakawa 1
PMCID: PMC5926299  PMID: 11123428

Abstract

Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM‐H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed α‐smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM‐H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture‐induced activation contained platelet‐derived growth factor (PDGF)‐AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF)β, and could augment LM‐H3‐cell proliferation and migration. Neutralizing antibodies against PDGF‐AA and PDGF‐BB and those against PDGF‐BB and HGF inhibited proliferation and migration, respectively, of LM‐H3 cells, whereas antibody against TGF‐β had no effect. LM‐H3 cells expressed PDGF receptors‐α and ‐β and c‐met. Conditioned medium of LM‐H3 cells contained PDGF‐AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti‐PDGF‐AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis.

Keywords: Platelet‐derived growth factor, Hepatocyte growth factor, Hepatic metastasis, Hepatic stellate cell, Colon carcinoma

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