Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction

Chie Kudo-Saito, Takafumi Fuwa, Kouichi Murakami, Yutaka Kawakami

研究成果: Article査読

46 被引用数 (Scopus)

抄録

Bone metastasis greatly deteriorates the quality of life in patients with cancer. Although mechanisms have been widely investigated, the relationship between cancer bone metastasis and antitumor immunity in the host has been much less studied. Here, we report a novel mechanism of bone metastasis mediated by FSTL1, a follistatinlike glycoprotein secreted by Snail+ tumor cells, which metastasize frequently to bone. We found that FSTL1 plays a dual role in bone metastasis-in one way by mediating tumor cell invasion and bone tropism but also in a second way by expanding a population of pluripotent mesenchymal stem-like CD45 ALCAM cells derived from bone marrow. CD45- ALCAM + cells induced bone metastasis de novo, but they also generated CD8low T cells with weak CTL activity in the periphery, which also promoted bone metastasis in an indirect manner. RNA interferencemediated attenuation of FSTL1 in tumor cells prevented bone metastasis along with the parallel increase in ALCAM+ cells and CD8low T cells. These effects were accompanied by heightened antitumor immune responses in vitro and in vivo. In clinical specimens of advanced breast cancer, ALCAM+ cells increased with FSTL1 positivity in tumor tissues, but not in adjacent normal tissues, consistent with a causal connection between these molecules. Our findings define FSTL1 as an attractive candidate therapeutic target to prevent or treat bone metastasis, which remains a major challenge in patients with cancer.

本文言語English
ページ(範囲)6185-6193
ページ数9
ジャーナルCancer Research
73
20
DOI
出版ステータスPublished - 2013 10 15

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

フィンガープリント

「Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル