Z Gastroenterol 2015; 53 - A4_34
DOI: 10.1055/s-0034-1397186

Mouse models of colorectal and mammary cancer liver metastases and microenvironmental interplay with tumor-associated macrophages (TAMs)

D Bocuk 1, P Krause 1, S Niebert 1, T Pukrop 2, T Beissbarth 3, M Ghadimi 1, S Koenig 1
  • 1University Medical Center, Goettingen, Department of General, Visceral, and Pediatric Surgery, Goettingen, Germany
  • 2University Medical Center, Goettingen, Department of Hematology and Oncology, Goettingen, Germany
  • 3University Medical Center, Goettingen, Department of Medical Statistics, Goettingen, Germany

Introduction:

Colorectal cancer (CRC) and breast cancer (BC) rank as two of the most common tumors in developed countries. Given the relatively frequent formation of liver metastases, investigation of the hepatic microenvironment is crucial. Here we present two new immunocompetent mouse models of liver metastases and the microenvironmental interplay of tumor cells with TAMs.

Methods:

The cancer cell lines 410.4 (mammary gland) and CMT-93 (colorectal) were implanted locally into the liver or via the portal vein of syngeneic mice to monitor the time-dependent progression into metastases. Immunostaining demonstrated the growth pattern of metastases and the heterogeneity of TAMs in different tumor compartments.

Results:

Local implantation of tumor cells resulted in circumscribed tumor masses while the intraportal implantation induced diffuse hepatic infiltration. CRC-derived metastases demonstrated differentiated (glandular: CD49f, beta-catenin) as well as undifferentiated areas (mesenchymal: vimentin and CD44), whereas BC metastases were mostly undifferentiated. Both tumor entities exhibited a tumor/liver interface marked by an increased density of inflammatory cells. M1 macrophages (tumoricidal activity) were mostly located within the liver metastases (CD11b+) as well as in the hepatic microenvironment (F4/80+ and CD68+). M2 macrophages (propagation of tumor progression) were mainly detectable in the hepatic microenvironment (CD163+).

Conclusion:

The presented animal models allow the investigation of the interaction of liver metastases with TAMs. In further studies, we will use these mouse models and compare the growth patterns and association of TAMs following genetic modification of the cancer cell lines with respect to the Wnt and EGFR signaling pathways.

Funded by the German Federal Ministry of Education and Research

(Bundesministerium für Bildung und Forschung, BMBF) e:Bio project MetastaSys

Corresponding author: Bocuk, Derya

E-Mail: derya.bocuk@med.uni-goettingen.de