Tumor Biology

, Volume 37, Issue 2, pp 2461–2471 | Cite as

The chemokines CCR1 and CCRL2 have a role in colorectal cancer liver metastasis

  • Israa G. Akram
  • Rania Georges
  • Thomas Hielscher
  • Hassan Adwan
  • Martin R. Berger
Original Article

Abstract

C-C chemokine receptor type 1 (CCR1) and chemokine C-C motif receptor-like 2 (CCRL2) have not yet been sufficiently investigated for their role in colorectal cancer (CRC). Here, we investigated their expression in rat and human CRC samples, their modulation of expression in a rat liver metastasis model, as well as the effects on cellular properties resulting from their knockdown. One rat and five human colorectal cancer cell lines were used. CC531 rat colorectal cells were injected via the portal vein into rats and re-isolated from rat livers after defined periods. Following mRNA isolation, the gene expression was investigated by microarray. In addition, all cell lines were screened for mRNA expression of CCR1 and CCRL2 by reverse transcription polymerase chain reaction (RT-PCR). Cell lines with detectable expression were used for knockdown experiments; and the respective influence was determined on the cells’ proliferation, scratch closure, and colony formation. Finally, specimens from the primaries of 50 patients with CRC were monitored by quantitative RT-PCR for CCR1 and CCRL2 expression levels. The microarray studies showed peak increases of CCR1 and CCRL2 in the early phase of liver colonization. Knockdown was sufficient at mRNA but only moderate at protein levels and resulted in modest but significant inhibition of proliferation (p < 0.05), scratch closure, and colony formation (p < 0.05). All human CRC samples were positive for CCR1 and CCRL2 and showed a significant pairwise correlation (p < 0.0004), but there was no correlation with tumor stage or age of patients. In summary, the data point to an important role of CCR1 and CCRL2 under conditions of organ colonization and both chemokine receptors qualify as targets of treatment during early colorectal cancer liver metastasis.

Keywords

Colorectal cancer progression Colorectal cancer cell lines Gene knockdown Liver colonization Chemokine receptors 

Notes

Conflicts of interest

None

Supplementary material

13277_2015_4089_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 15 kb)
13277_2015_4089_MOESM2_ESM.docx (15 kb)
ESM 2 (DOCX 14 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Israa G. Akram
    • 1
    • 2
  • Rania Georges
    • 1
    • 3
  • Thomas Hielscher
    • 4
  • Hassan Adwan
    • 1
    • 5
  • Martin R. Berger
    • 1
  1. 1.Toxicology and Chemotherapy UnitGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.College of Science, Chemistry DepartmentAl-Mustansirya UniversityBaghdadIraq
  3. 3.Department of Pharmacology and ToxicologyAl-Baath UniversityHomsSyria
  4. 4.Department of BiostatisticsGerman Cancer Research Center (DKFZ)HeidelbergGermany
  5. 5.Department of Pharmacology and ToxicologyGerman University of CairoCairoEgypt

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