Lyve-1 expressing perivascular macrophages orchestrate pericyte expansion to sustain angiogenesis in cancer

Opzoomer, J. W.; Anstee, J. E.; Dean, I.; Hill, E. J.; Bouybayoune, I.; Caron, J.; Muliaditan, T.; Gordon, P.; Nuamah, R.; Pinder, S. E.; Ng, T.; Dazzi, F.; Kordasti, S.; Withers, D. R.; Lawrence, T.; Arnold, J. N.

doi:10.1101/2020.10.30.361907

bioRxiv · 10.1101/2020.10.30.361907

Lyve-1 expressing perivascular macrophages orchestrate pericyte expansion to sustain angiogenesis in cancer

Opzoomer, J. W.·Anstee, J. E.·Dean, I.·Hill, E. J.·Bouybayoune, I.·Caron, J.·Muliaditan, T.·Gordon, P.·Nuamah, R.·Pinder, S. E.·Ng, T.·Dazzi, F.·Kordasti, S.·Withers, D. R.·Lawrence, T.·Arnold, J. N.

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Abstract

Tumor associated macrophages (TAMs) are a highly plastic stromal cell type which support cancer progression. Using single-cell RNA-sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT) we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) which spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+ TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells which express alpha-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+ TAMs in orchestrating a selective platelet-derived growth factor-CC-dependent expansion of the perivascular mesenchymal population, creating a pro-angiogenic niche. This study highlights the inter-reliance of the immune and non-immune stromal network which support cancer progression and provides therapeutic opportunities for tackling the disease.

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Opzoomer, J. W., Anstee, J. E., Dean, I., Hill, E. J., Bouybayoune, I., Caron, J., Muliaditan, T., Gordon, P., Nuamah, R., Pinder, S. E., Ng, T., Dazzi, F., Kordasti, S., Withers, D. R., Lawrence, T., Arnold, J. N.. 2020-10-30. Lyve-1 expressing perivascular macrophages orchestrate pericyte expansion to sustain angiogenesis in cancer. https://doi.org/10.1101/2020.10.30.361907

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