Research by Mike Millar consultant and (Histology Chief Technical Officer) at Concept Life Sciences (Edinburgh) has published in Cancer Cell. This was a multi group collaborative effort led by Dr Luca Cassetta (Post-Doctoral Researcher) and Prof. Jeff Pollard (Director, Centre for Reproductive Health) from the University of Edinburgh. Mike is also the Histology and Imaging Facility Research Manager at the University of Edinburgh.
The paper entitled “Human Tumour-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets”, which made the journal front cover, discusses the roles of tumour-associated macrophages (TAMs) and circulating monocytes in human cancer, which currently are poorly understood. The research shows that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. The data show that TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. It is reported that a breast cancer TAM signature, which is highly enriched in aggressive breast cancer subtypes, is associated with shorter disease-specific survival.
Mike’s research demonstrated the co-expression of protein biomarkers SIGLEC1 and CD163, and the mRNA biomarker CCL8, using a fluorescent based protein colocalization assay (fluorescent tyramides) combined with mRNA detection using RNAscope. This allowed the quantification of cell populations within cancer tissue sections by image analysis (Figure 1).
Figure 1. TAMs and Cancer Cells Engage in Cytokine Feedback Loops to Support CCL8 and SIGLEC1 Expression in Breast Cancer TAMs (Pollard et al., 2019). IF and fluorescence in situ hybridization for CCL8 mRNA (top) or a DapB-control RNA (bottom) in breast cancer samples. Scale bars, 10 mm (n = 3). Inset representing a SIGLEC1+CD163+ macrophage-expressing CCL8 mRNA (top) or DapB-control mRNA (bottom). XY, XZ, and YZ projections are shown (right panels).
Commenting on this research undertaken, our Group Head of Translational Biology Prof. Steve Anderton had the following to say “As a leading CRO, Concept Life Sciences are continually looking to develop scientific expertise and technical understanding to ensure we can offer the most advanced services to our clients. This work by Mike in collaboration with leading academics at the University of Edinburgh is typical of our science-led academic approach offered to industrial standards, ensuring we deliver cutting-edge work programmes for our clients.”
To read the full article click here
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets. Cassetta L, Fragkogianni S, Sims AH, Swierczak A, Forrester LM, Zhang H, Soong DYH, Cotechini T, Anur P, Lin EY, Fidanza A, Lopez-Yrigoyen M, Millar MR, Urman A, Ai Z, Spellman PT, Hwang ES, Dixon JM, Wiechmann L, Coussens LM, Smith HO, Pollard JW. Cancer Cell. 2019 Apr 15;35(4):588-602.e10.