TY - JOUR
T1 - Innate immune cell-derived microparticles facilitate hepatocarcinoma metastasis by transferring integrin αmβ2 to tumor cells
AU - Ma, Jingwei
AU - Cai, Wenqian
AU - Zhang, Yi
AU - Huang, Chunmei
AU - Zhang, Huafeng
AU - Liu, Jing
AU - Tang, Ke
AU - Xu, Pingwei
AU - Katirai, Foad
AU - Zhang, Jianmin
AU - He, Wei
AU - Ye, Duyun
AU - Shen, Guan Xin
AU - Huang, Bo
PY - 2013/9/15
Y1 - 2013/9/15
N2 - Mechanisms by which tumor cells metastasize to distant organs still remain enigmatic. Immune cells have been assumed to be the root of metastasis by their fusing with tumor cells. This fusion theory, although interpreting tumor metastasis analogically and intriguingly, is arguable to date. We show in this study an alternative explanation by immune cell-derived microparticles (MPs). Upon stimulation by PMA or tumor cell-derived supernatants, immune cells released membrane-based MPs, which were taken up by H22 tumor cells, leading to tumor cell migration in vitro and metastasis in vivo. The underlying molecular basis was involved in integrin αMβ2 (CD11b/CD18), which could be effectively relayed from stimulated innate immune cells to MPs, then to tumor cells. Blocking either CD11b or CD18 led to significant decreases in MP-mediated tumor cell metastasis. This MP-mediated transfer of immune phenotype to tumor cells might also occur in vivo. These findings suggest that tumor cells may usurp innate immune cell phenotypes via MP pathway for their metastasis, providing new insight into tumor metastatic mechanism.
AB - Mechanisms by which tumor cells metastasize to distant organs still remain enigmatic. Immune cells have been assumed to be the root of metastasis by their fusing with tumor cells. This fusion theory, although interpreting tumor metastasis analogically and intriguingly, is arguable to date. We show in this study an alternative explanation by immune cell-derived microparticles (MPs). Upon stimulation by PMA or tumor cell-derived supernatants, immune cells released membrane-based MPs, which were taken up by H22 tumor cells, leading to tumor cell migration in vitro and metastasis in vivo. The underlying molecular basis was involved in integrin αMβ2 (CD11b/CD18), which could be effectively relayed from stimulated innate immune cells to MPs, then to tumor cells. Blocking either CD11b or CD18 led to significant decreases in MP-mediated tumor cell metastasis. This MP-mediated transfer of immune phenotype to tumor cells might also occur in vivo. These findings suggest that tumor cells may usurp innate immune cell phenotypes via MP pathway for their metastasis, providing new insight into tumor metastatic mechanism.
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U2 - 10.4049/jimmunol.1300171
DO - 10.4049/jimmunol.1300171
M3 - Article
C2 - 23956429
AN - SCOPUS:84884269031
SN - 0022-1767
VL - 191
SP - 3453
EP - 3461
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -