The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumours and metastatic tumour foci.
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.
DuPré
Sally A
SA
Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV 89557, USA. sdupre@unr.nevada.edu
Redelman
Doug
D
Hunter
Kenneth W
KW
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology* / Q000556:secondary*; D039481:CD11b Antigen / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics; D054405:Chemokine CCL3 / Q000235:genetics; D054407:Chemokine CCL4 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D054360:Chemokine CXCL1 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007955:Leukemoid Reaction; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology*; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D039481:CD11b Antigen; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D012333:RNA, Messenger