Bone marrow derived "fibrocytes" contribute to tumor proliferation and fibrosis in gastric cancer

被引:38
作者
Terai, Shiro [1 ]
Fushida, Sachio [1 ]
Tsukada, Tomoya [1 ]
Kinoshita, Jun [1 ]
Oyama, Katsunobu [1 ]
Okamoto, Koichi [1 ]
Makino, Isamu [1 ]
Tajima, Hidehiro [1 ]
Ninomiya, Itasu [1 ]
Fujimura, Takashi [1 ]
Harada, Shinichi [2 ]
Ohta, Tetsuo [1 ]
机构
[1] Kanazawa Univ, Dept Surg Gastroenterol, Grad Sch Med Sci, Kanazawa, Ishikawa 9208641, Japan
[2] Kanazawa Univ, Ctr Biomed Res & Educ, Grad Sch Med Sci, Kanazawa, Ishikawa 9208641, Japan
基金
日本学术振兴会;
关键词
Fibrocytes; Bone marrow-derived cell; Cancer associated fibroblasts; Cancer stroma; Gastric cancer; CIRCULATING FIBROCYTES; TGF-BETA; DIFFERENTIATION; MYOFIBROBLASTS; FIBROBLASTS;
D O I
10.1007/s10120-014-0380-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer-associated fibroblasts (CAFs) in the stroma are considered to play important roles for gastric cancer proliferation, invasion, and fibrosis, but the source of CAFs and their interaction with cancer cells in the microenvironment have not been fully determined. Here we elucidated the role of bone marrow-derived cells, fibrocytes, in development of gastric cancers, as represented by scirrhous gastric cancer. In co-culturing MKN45 gastric cancer cells and purified fibrocytes from healthy volunteers, migration and endothelial mesenchymal transition associated gene expression were evaluated using western blot analysis. Also, mouse xenograft models of MKN45 with or without fibrocytes were conducted to investigate their tumorigenicity and immunohistological differences of tumors. Co-culture of fibrocytes with MKN45 resulted in morphological changes from cobblestone-shape to spindle-shape and enhanced expression of alpha-SMA and collagen type I in fibrocytes, suggesting that co-culture with gastric cancer cells may have induced the differentiation of fibrocytes to myofibroblasts. Furthermore, enhanced expression of SDF-1 in MKN45 and CXCR4 in fibrocytes were also determined. Mouse xenograft models inoculated with MKN45 and fibrocytes revealed significantly larger tumors than those inoculated with MKN45 cells alone, and the stroma in co-inoculated tumors consisted of myofibroblasts and fibrosis. Mouse-derived cells expressing both CD45 and type I collagen were also observed in co-inoculated tumors. Fibrocytes derived from bone marrow may migrate into the microenvironment of gastric cancer by SDF-1/CXCR4 system, and enhance the tumor proliferation and fibrosis as CAFs.
引用
收藏
页码:306 / 313
页数:8
相关论文
共 26 条
[1]   Peripheral blood fibrocytes: Differentiation pathway and migration to wound sites [J].
Abe, R ;
Donnelly, SC ;
Peng, T ;
Bucala, R ;
Metz, CN .
JOURNAL OF IMMUNOLOGY, 2001, 166 (12) :7556-7562
[2]   The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses [J].
Bellini, Alberto ;
Mattoli, Sabrina .
LABORATORY INVESTIGATION, 2007, 87 (09) :858-870
[3]   CIRCULATING FIBROCYTES DEFINE A NEW LEUKOCYTE SUBPOPULATION THAT MEDIATES TISSUE-REPAIR [J].
BUCALA, R ;
SPIEGEL, LA ;
CHESNEY, J ;
HOGAN, M ;
CERAMI, A .
MOLECULAR MEDICINE, 1994, 1 (01) :71-81
[4]   Inflammation and cancer [J].
Coussens, LM ;
Werb, Z .
NATURE, 2002, 420 (6917) :860-867
[5]   Stromal myofibroblasts are drivers of invasive cancer growth [J].
De Wever, Olivier ;
Demetter, Pieter ;
Mareel, Marc ;
Bracke, Marc .
INTERNATIONAL JOURNAL OF CANCER, 2008, 123 (10) :2229-2238
[6]   Differential impact of TGF-β and EGF on fibroblast differentiation and invasion reciprocally promotes colon cancer cell invasion [J].
Denys, Hannelore ;
Derycke, Lara ;
Hendrix, An ;
Westbroek, Wendy ;
Gheldof, Alexander ;
Narine, Kishan ;
Pauwels, Patrick ;
Gespach, Christian ;
Bracke, Marc ;
De Wever, Olivier .
CANCER LETTERS, 2008, 266 (02) :263-274
[7]   Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts [J].
Direkze, NC ;
Hodivala-Dilke, K ;
Jeffery, R ;
Hunt, T ;
Poulsom, R ;
Oukrif, D ;
Alison, MR ;
Wright, NA .
CANCER RESEARCH, 2004, 64 (23) :8492-8495
[8]   Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells [J].
Fuyuhiro, Y. ;
Yashiro, M. ;
Noda, S. ;
Kashiwagi, S. ;
Matsuoka, J. ;
Doi, Y. ;
Kato, Y. ;
Hasegawa, T. ;
Sawada, T. ;
Hirakawa, K. .
BRITISH JOURNAL OF CANCER, 2011, 105 (07) :996-1001
[9]   Cancer-associated orthotopic myofibroblasts stimulates the motility of gastric carcinoma cells [J].
Fuyuhiro, Yuhiko ;
Yashiro, Masakazu ;
Noda, Satoru ;
Matsuoka, Junko ;
Hasegawa, Tsuyoshi ;
Kato, Yukihiro ;
Sawada, Tetsuji ;
Hirakawa, Kosei .
CANCER SCIENCE, 2012, 103 (04) :797-805
[10]   Fibrocytes in health and disease [J].
Herzog, Erica L. ;
Bucala, Richard .
EXPERIMENTAL HEMATOLOGY, 2010, 38 (07) :548-556