Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

The role of CCL2 in mammary gland development and cancerĀ  (#311)

Xuan Sun 1 2 , Sarah Robertson 1 2 , Wendy Ingman 1 2 3
  1. Obstetrics and Gynaecology, The University of Adelaide, Adelaide, SA, Australia
  2. Robinson institute, Adelaide
  3. Discipline of Surgery, School of Medicine , The Queen Elizabeth Hospital, Adelaide

Chemokine ligand 2 (CCL2) is a pro-inflammatory cytokine and a highly potent chemoattractant for monocytes and macrophages to sites of tissue injury and inflammation. CCL2 expression has not been documented in human non-neoplastic breast, however, in breast carcinomas CCL2 can be highly expressed by the tumour and surrounding stromal cells. Utilising immunohistochemical techniques, we have demonstrated that non-neoplastic breast tissue exhibits variable expression of CCL2 in the epithelium, with protein abundance ranging from none to moderate. To investigate the role of CCL2 in mammary gland development and cancer susceptibility, transgenic mice in which CCL2 overexpression is driven by the mammary gland epithelial cell specific mouse mammary tumour virus (MMTV) promoter (Ccl2-Mmtv) were generated. Increased abundance of mRNA encoding CCL2 is observed in both the mammary glands and salivary glands of Ccl2-Mmtv mice, and F4/80 positive macrophages are observed in increased abundance in the stroma surrounding mammary epithelium in Ccl2-Mmtv transgenic mice compared to non-transgenic FVB control mice. To investigate the role of CCL2 in mammary gland development, the mammary glands were dissected from 12 week old Ccl2-Mmtv and FVB mice at proestrus, estrus, metestrus and diestrus. Increased abundance of alveolar epithelium was observed in H&E stained paraffin-embedded sections from Ccl2-Mmtv mice compared to FVB mice at proestrus and diestrus (p<0.05). To investigate the role of CCL2 in mammary gland tumourigenesis, both Ccl2-Mmtv and FVB mice were administered DMBA carcinogen by oral gavage, a well-described method to investigate mammary tumour susceptibility. An increased incidence of mammary tumour formation and decreased tumour latency in Ccl2-Mmtv mice was observed, compared to FVB mice (p<0.05). These studies indicate that epithelial cell-derived CCL2 drives macrophage recruitment to the mammary gland, alveolar epithelial cell development and increased mammary tumour susceptibility.