The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumours and metastatic tumour foci

• Published in: International journal of experimental pathology Vol. 88; no. 5; pp. 351 - 360
• Main Authors: DuPre´, Sally A., Redelman, Doug, Hunter Jr, Kenneth W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007
• Subjects: 4T1; Animals; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Breast Neoplasms - secondary; carcinoma; CD11b Antigen - immunology; Chemokine CCL2 - genetics; Chemokine CCL3 - genetics; Chemokine CCL4 - genetics; Chemokine CCL5 - genetics; Chemokine CXCL1 - genetics; chemokines; Disease Progression; Female; Flow Cytometry - methods; Gene Expression; Humans; Immunophenotyping; infiltrates; Leukemoid Reaction; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - secondary; mammary; Mammary Neoplasms, Animal - immunology; Mammary Neoplasms, Animal - pathology; Mammary Neoplasms, Animal - secondary; Mice; Mice, Inbred BALB C; Myeloid Cells - immunology; Myeloid Cells - pathology; Neoplasm Transplantation; Original; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tumor Cells, Cultured
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1111/j.1365-2613.2007.00539.x

Summary The murine mammary carcinoma 4T1 causes a leukemoid reaction with profound granulocytosis coincident with the production of tumour‐derived growth factors. Here, we study the evolving cellular landscape of primary tumours and metastatic tumour foci and correlate haematopoietic cell infiltration with the production of tumour‐derived chemokines. Flow cytometric analysis of enzyme digested primary tumours at different times after transplantation revealed a progressively increasing CD45+ haematopoietic cell infiltrate consisting predominantly of CD11b+ myeloid cells. Most of these cells had an F4/80+/CD11c+ phenotype, many of which also stained Gr‐1+. Smaller numbers of Gr‐1+CD11b+ granulocytes and lymphoid cells were also identified. Progressive increases in Gr‐1+ granulocytes were observed in enzymatic digests of livers and lungs with metastatic tumour foci. Cultured 4T1 tumour cells expressed mRNA transcripts for the myeloid cell chemokines RANTES, MCP‐1 and KC, and enzymatically digested cells from primary 4T1 tumours partially depleted of CD45+ cells expressed transcripts for these chemokines and also MIP‐1α and MIP‐1β. These data demonstrate that 4T1 tumour‐bearing mice have mixed myeloid cell infiltrates of primary tumours and granulocytic infiltrates of metastatic organs. This pathologic presentation correlated with the expression of tumour‐derived chemokines.