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

Abstract

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.

• Authors: Sally A DuPré, Doug Redelman, Kenneth W Hunter Jr
• Journal: International journal of experimental pathology (Int J Exp Pathol) Vol. 88 Issue 5 Pg. 351-60 (Oct 2007) ISSN: 0959-9673 [Print] England
• PMID: 17877537 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Breast Neoplasms (immunology, pathology, 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, pathology, secondary)
• Lung Neoplasms (immunology, pathology, secondary)
• Mammary Neoplasms, Animal (immunology, pathology, secondary)
• Mice
• Mice, Inbred BALB C
• Myeloid Cells (immunology, pathology)
• Neoplasm Transplantation
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured