Related Experiment Video
Updated: May 8, 2026
Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model
Published on: November 26, 2010
Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction
Chie Kudo-Saito1, Takafumi Fuwa, Kouichi Murakami
1Authors' Affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Abstract:
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 follistatin-like 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 CD8(low) T cells with weak CTL activity in the periphery, which also promoted bone metastasis in an indirect manner. RNA interference-mediated attenuation of FSTL1 in tumor cells prevented bone metastasis along with the parallel increase in ALCAM(+) cells and CD8(low) 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.
Insights
Follistatin-like glycoprotein 1 (FSTL1) promotes cancer bone metastasis by altering immune cells. Inhibiting FSTL1 may prevent metastasis and enhance antitumor immunity.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Bone metastasis significantly impacts cancer patient quality of life.
- The interplay between cancer bone metastasis and host antitumor immunity is poorly understood.
- Follistatin-like glycoprotein 1 (FSTL1) is implicated in cancer progression.
Purpose of the Study:
- To elucidate the role of FSTL1 in cancer bone metastasis.
- To investigate the mechanism by which FSTL1 influences antitumor immunity.
- To identify FSTL1 as a potential therapeutic target for bone metastasis.
Main Methods:
- Investigated FSTL1's role in bone metastasis using in vitro and in vivo models.
- Analyzed the impact of FSTL1 on mesenchymal stem-like cells (CD45(-)ALCAM(+)) and T cells (CD8(low)).
- Utilized RNA interference to attenuate FSTL1 expression and assessed antitumor immune responses.
- Examined clinical specimens of advanced breast cancer for FSTL1 and ALCAM(+) cell correlation.
Main Results:
- FSTL1 mediates tumor cell invasion and bone tropism.
- FSTL1 expands CD45(-)ALCAM(+) cells, which induce de novo bone metastasis.
- FSTL1 promotes the generation of CD8(low) T cells with suppressed cytotoxic T lymphocyte (CTL) activity, indirectly aiding metastasis.
- FSTL1 inhibition prevented bone metastasis, increased ALCAM(+) cells and CD8(low) T cells, and enhanced antitumor immunity.
- Clinical data showed a positive correlation between FSTL1 and ALCAM(+) cells in advanced breast cancer tissues.
Conclusions:
- FSTL1 plays a critical dual role in promoting bone metastasis through direct tumor cell effects and indirect immune modulation.
- Targeting FSTL1 offers a promising strategy to combat cancer bone metastasis and bolster host antitumor immunity.
