title: ASF-4-1 fibroblast-rich culture increases chemoresistance and mTOR expression of pancreatic cancer BxPC-3 cells at the invasive frontin vitro, and promotes tumor growth and invasionin vivo.
abstract: Pancreatic cancer develops dense stromal tissue through the desmoplastic reaction. The aim of the present study was to assess the effects of a fibroblast-rich environment on the malignant potential of pancreatic cancer. Cells from the human pancreatic cancer cell line BxPC-3 were mixed at a ratio of 1:3 (fibroblast-rich) or 1:1 (fibroblast-poor) with cells from the human skin fibroblast line ASF-4-1. In the fibroblast-rich co-culture, tumor budding was observed and BxPC-3 cells were found to be more resistant to gemcitabine than those in the fibroblast-poor co-culture. Immunohistochemistry revealed that the expression of mammalian target of rapamycin was increased at the invasive front of fibroblast-rich co-cultures. In addition, in mouse xenografts of fibroblast-rich co-cultures, tumors were larger and had a higher Ki-67 index compared with that of the fibroblast-poor co-culture xenografts. These results indicate that fibroblast-rich co-cultures may promote the malignant potential of the pancreatic cancer cell line BxPC-3, bothin vitroandin vivo.
authors.affiliation: Department of Oncological Pathology, Institute of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Oncological Pathology, Institute of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kanayama
authors.affiliation: Department of Oncological Pathology, Institute of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshifumi S
authors.initials: YS
authors.lastname: Hirokawa
authors.affiliation: Department of Oncological Pathology, Institute of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Shiraishi
keywords: budding; fibroblast; mTOR; pancreatic cancer; three-dimensional co-culture