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.