Senescent mesenchymal stem cells promote colorectal cancer cells growth via galectin-3 expression.
BACKGROUND
Cellular senescence is linked to aging and tumorigenesis. The senescence of mesenchymal stem cells (MSCs) may influence the tumor growth, metastasis, and angiogenesis by secreting a variety of cytokines and growth factors.


RESULTS
The conditioned media of adipose derived MSCs (AD-MSCs) stimulated the proliferation of human LoVo colorectal-cancer cells, and the replicative senescent MSCs had the more obvious effects in comparison to that of premature AD-MSCs. Analysis of the factors secreted in the MSCs culture media determined that senescent MSCs expressed and secreted high levels of galectin-3. Galectin-3 expression correlated with the stimulatory effect of senescent AD-MSCs on LoVo cells proliferation, as knockdown of galectin-3 in senescent AD-MSCs significantly reversed the effect of MSCs-mediated growth stimulation of LoVo cells. Furthermore, the simultaneous addition of recombinant galectin-3 to the co-culture systems partially restored the tumor-promoting effect of the senescent AD-MSCs. Analysis of the mechanisms of senescent MSCs and galectin-3 on LoVo cells signal transduction determined that senescent MSCs and exogenous galectin-3 promoted cell growth by activating the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated kinase [ERK]1/2) pathway.


CONCLUSIONS
Senescent MSCs may alter the tissue microenvironment and affect nearby malignant cells via cytokine secretion, and galectin-3 is an important mediator of senescent AD-MSC-mediated stimulation of colon cancer cell growth. Therefore, thorough assessment of AD-MSCs prior to their implementation in clinical practice is warranted.
Department of Hematology, Affiliated Hospital of Guiyang Medical College, No. 28, Guiyi Street, Yunyan District, Guiyang, Guizhou Province 550004 China.
Yanju
Y
Li
Skin Regeneration Department of General Hospital of Chinese Armed Police, No. 69 Yongding Road, Haidian District, Beijing, 100039 China.
Xiao
X
Xu
Department of Hematology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Hematology, Hebei Institution of Hematology, 215 West Heping Road, Shijiazhuang City, Hebei Province 050000 China.
Lihua
L
Wang
Yanzhou Hospital of Traditional Chinese Medicine, No. 43 Dongqiao North Road, Yanzhou District, Jining, Shandong Province 272100 China.
Guangjin
G
Liu
Department of Hematology, Affiliated Hospital of Guiyang Medical College, No. 28, Guiyi Street, Yunyan District, Guiyang, Guizhou Province 550004 China.
Yanqi
Y
Li
Department of Hematology, Affiliated Hospital of Guiyang Medical College, No. 28, Guiyi Street, Yunyan District, Guiyang, Guizhou Province 550004 China.
Xiaobing
X
Wu
Department of Hematology, Affiliated Hospital of Guiyang Medical College, No. 28, Guiyi Street, Yunyan District, Guiyang, Guizhou Province 550004 China.
Yongguang
Y
Jing
Yanzhou Hospital of Traditional Chinese Medicine, No. 43 Dongqiao North Road, Yanzhou District, Jining, Shandong Province 272100 China.
Haiyan
H
Li
Department of Hematology, Affiliated Hospital of Guiyang Medical College, No. 28, Guiyi Street, Yunyan District, Guiyang, Guizhou Province 550004 China.
Guihua
G
Wang
Cellular senescence; Galectin-3; LoVo cells; Mesenchymal stem cells