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

Int J Exp Pathol. 2007 Oct;88(5):351-60. doi: 10.1111/j.1365-2613.2007.00539.x.


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-1alpha and MIP-1beta. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / secondary*
  • CD11b Antigen / immunology
  • Chemokine CCL2 / genetics
  • Chemokine CCL3 / genetics
  • Chemokine CCL4 / genetics
  • Chemokine CCL5 / genetics
  • Chemokine CXCL1 / genetics
  • Disease Progression
  • Female
  • Flow Cytometry / methods
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Leukemoid Reaction
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • 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
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • CD11b Antigen
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • RNA, Messenger