AI Article Synopsis
- Liver metastasis occurs in around 50% of colorectal cancer patients, and targeting the chemokine receptor 5 (CCR5) may offer a new treatment approach.
- The research involved using siRNAs and the FDA-approved drug maraviroc to study the effects of targeting CCR5 in various CRC models, both in cells and in an animal model that simulates liver metastasis.
- Results demonstrated that inhibiting CCR5 reduced cancer cell growth and spread, while in vivo treatment with maraviroc significantly decreased liver metastasis, highlighting CCR5 as a promising therapeutic target for colorectal cancer.
Article Abstract
Purpose: Liver metastasis is observed in up to 50% of colorectal cancer (CRC) patients. Available treatment options are limited and disease recurrence is often. Chemokine receptor 5 (CCR5) has attracted attention as novel therapeutic target for treating cancers. In this study, we reinforced the importance of CCR5 as therapeutic target in CRC and its liver metastasis by applying in vitro, in vivo and clinical investigations.
Methods: By targeting CCR5 via siRNAs or an FDA approved antagonist (maraviroc), we investigated the ensuing antineoplastic effects in three CRC cell lines. An animal model for CRC liver metastasis was used to evaluate time-dependent expressional modulation of the CCR5 axis by cDNA microarray. The model was also used to evaluate the in vivo efficacy of targeting CCR5 by maraviroc. Circulatory and tumor associated levels of CCR5 and its cognate ligands (CCL3, CCL4, CCL5) were analyzed by ELISA, qRT-PCR and immunohistochemistry.
Results: Targeting the CCR5 inhibited proliferative, migratory and clonogenic properties and interfered with cell cycle-related signaling cascades. In vivo findings showed significant induction of the CCR5 axis during the early liver colonization phase. Treatment with maraviroc significantly inhibited CRC liver metastasis in the animal model. Differential expression profiles of circulatory and tumor associated CCR5/ligands were observed in CRC patients and healthy controls.
Conclusion: The findings indicate that targeting the CCR5 axis can be an effective strategy for treating CRC liver metastasis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810651 | PMC |
| http://dx.doi.org/10.1007/s00432-020-03382-9 | DOI Listing |
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