Background & Aims
Development of liver metastases is a frequent complication in patients with colorectal
cancer (CRC), even after successful resection of the primary tumor. As such, post-operative
adjuvant therapies that aim to eliminate residual disease after surgery may improve
patient outcome.
Methods
We used a colon carcinoma liver metastases model, in which CC531s colon carcinoma
cells are injected into the portal circulation by a surgical procedure. As injected
tumor cells are arrested in the liver, this model is suitable for investigating the
interaction of tumor cells with the liver microenvironment. By administering tumor
specific monoclonal antibodies (mAb) directly post-operatively, we were able to determine
the effect of antibody therapy on eradication of arrested tumor cells and subsequent
liver metastases outgrowth.
Results
We showed that post-operative treatment with tumor specific monoclonal antibodies
(mAb) prevents liver metastases outgrowth. Antibody-dependent phagocytosis (ADPh)
was the main mechanism involved, as enhanced uptake of tumor cells by innate mononuclear
phagocytes in the liver was observed after mAb therapy. Furthermore, Kupffer cells
(KC) were identified as the most prominent effector cells, as depletion of KC abolished
therapeutic efficacy. This was partly compensated by monocytes when animals were treated
with a high mAb dose, but monocytes were unable to phagocytose tumor cells when rats
were treated with low mAb doses.
Conclusions
The finding that KC and monocytes can eliminate tumor cells through ADPh has important
and promising clinical implications for designing new adjuvant therapies for patients
undergoing CRC resection.
Abbreviations:
ADCC (antibody dependent cellular cytotoxicity), ADPh (antibody dependent phagocytosis), CRC (colorectal cancer), FcγR (Fc gamma receptor), FCS (fetal calf serum), Ig (immunoglobulin), i.p. (intraperitoneal), KC (Kupffer cell), mAb (monoclonal antibody), NK (natural killer)Keywords
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Article info
Publication history
Published online: June 25, 2010
Identification
Copyright
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
