Semaphorin3F down-regulates the expression of integrin alpha(v)beta3 and sensitizes multicellular tumor spheroids to chemotherapy via the neuropilin-2 receptor in vitro.
BACKGROUND
Multicellular resistance (MCR), i.e. decreased sensitivity to anticancer drugs compared with common monolayer cell (MC) cultures, depends partly on tumor cell-cell adhesion. Previous studies have shown that anti-adhesive therapies, including integrin alpha(v), beta(1) and alpha(v)beta(3) targeting, induced apoptosis and reversed the sensitivity of MCR.


METHODS
A model of three-dimensional cell culture was used to establish HT29 multicellular spheroid cells (MCS) and explore the effect of semaphorin3F (Sema3F) on integrin-mediated cell-cell interactions in MCS of a human colorectal adenocarcinoma cell line (HT29) and sensitization of HT29 MCS to 5-fluorouracil and oxaliplatin via a decrease in integrin alpha(v)beta(3).


RESULTS
Elevated expression of Sema3F led to the up-regulation neuropilin-2 (Nrp2) receptor expression and the down-regulation of integrin alpha(v)beta(3) expression. Furthermore, short interfering RNA of Nrp2 could reverse MCR.


CONCLUSIONS
Our study demonstrates that Sema3F can sensitize MCR by decreasing integrin alpha(v)beta(3)expression via the Nrp2 receptor.
Zheng
Chenhong
C
Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Zhou
Qi
Q
Wu
Feng
F
Peng
Qiuping
Q
Tang
Airong
A
Liang
Houjie
H
Zeng
Yanjun
Y
D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism*; D018874:Spheroids, Cellular
D039302:Integrin alphaVbeta3; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C491230:SEMA3F protein, human