TY - JOUR
T1 - Macrophage conditioned medium promotes colorectal cancer stem cell phenotype via the hedgehog signaling pathway
AU - Fan, Fan
AU - Wang, Rui
AU - Boulbes, Delphine R.
AU - Zhang, Huiyuan
AU - Watowich, Stephanie S.
AU - Xia, Ling
AU - Ye, Xiangcang
AU - Bhattacharya, Rajat
AU - Ellis, Lee M.
N1 - Publisher Copyright:
© 2018 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/1
Y1 - 2018/1
N2 - Background There is conflicting data on the role of macrophages in colorectal cancer (CRC); some studies have shown that macrophages can exert an anti-tumor effect whereas others show that macrophages are tumor promoting. We sought to determine the role of conditioned medium (CM) from macrophages, in particular classically activated macrophages, on the development of the CSC phenotype in CRC cells, which is believed to mediate tumor growth and chemoresistance. Methods Murine (CT26) and human (HCP-1) CRC cell lines were treated with CM from lipopolysaccharide (LPS)-activated murine macrophages. The CSC population was assessed using the sphere-forming assay and aldehyde dehydrogenase assay. Chemoresistance studies were performed using the MTT assay. CSC transcription factors and SHH protein were analyzed by Western blotting. Results The results showed that LPS-activated macrophage CM induced the CSC phenotype in CRC cells. Further studies showed that the CSC phenotype was mediated by the sonic hedgehog (SHH)-Gli signaling pathway, which is known to drive self-renewal; these effects were blocked by depletion of SHH in macrophage CM. In addition, LPS-activated macrophage CM enhanced chemoresistance. Conclusions LPS-activated macrophages play an active role in promoting the CSC phenotype through activation of the SHH-Gli signaling pathway in CRC cells.
AB - Background There is conflicting data on the role of macrophages in colorectal cancer (CRC); some studies have shown that macrophages can exert an anti-tumor effect whereas others show that macrophages are tumor promoting. We sought to determine the role of conditioned medium (CM) from macrophages, in particular classically activated macrophages, on the development of the CSC phenotype in CRC cells, which is believed to mediate tumor growth and chemoresistance. Methods Murine (CT26) and human (HCP-1) CRC cell lines were treated with CM from lipopolysaccharide (LPS)-activated murine macrophages. The CSC population was assessed using the sphere-forming assay and aldehyde dehydrogenase assay. Chemoresistance studies were performed using the MTT assay. CSC transcription factors and SHH protein were analyzed by Western blotting. Results The results showed that LPS-activated macrophage CM induced the CSC phenotype in CRC cells. Further studies showed that the CSC phenotype was mediated by the sonic hedgehog (SHH)-Gli signaling pathway, which is known to drive self-renewal; these effects were blocked by depletion of SHH in macrophage CM. In addition, LPS-activated macrophage CM enhanced chemoresistance. Conclusions LPS-activated macrophages play an active role in promoting the CSC phenotype through activation of the SHH-Gli signaling pathway in CRC cells.
UR - http://www.scopus.com/inward/record.url?scp=85039967162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039967162&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0190070
DO - 10.1371/journal.pone.0190070
M3 - Article
C2 - 29293549
AN - SCOPUS:85039967162
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 1
M1 - e0190070
ER -