2. Academic Validation
  3. Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1

Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1

  • Commun Biol. 2020 Sep 22;3(1):524. doi: 10.1038/s42003-020-01246-z.
Venkatesh Krishnan 1,  Supreeti Tallapragada 1,  Bruce Schaar 2,  Kalika Kamat 1,  Anita M Chanana 3,  Yue Zhang 4,  Sonia Patel 5,  Vinita Parkash 6,  Carrie Rinker-Schaeffer 7,  Ann K Folkins 8,  Erinn B Rankin 1 9,  Oliver Dorigo 10 11
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford School of Medicine, Stanford Cancer Institute, Stanford, CA, USA.
  • 2 Genome Technology Center, Stanford, CA, USA.
  • 3 Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • 4 Department of Physiology and Chemistry, Genentech, San Francisco, CA, USA.
  • 5 Department of Thoracic Head and Neck Medical Oncology, Division of Cancer Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • 6 Department of Pathology, Yale School of Medicine and Yale School of Public Health, New Haven, CT, USA.
  • 7 Department of Surgery, Division of Urology, University of Chicago, Chicago, IL, USA.
  • 8 Department of Pathology, Stanford School of Medicine, Stanford, CA, USA.
  • 9 Department of Radiation Oncology, Stanford School of Medicine, Stanford, CA, USA.
  • 10 Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford School of Medicine, Stanford Cancer Institute, Stanford, CA, USA. odorigo@stanford.edu.
  • 11 Stanford Women's Cancer Center, Stanford, CA, USA. odorigo@stanford.edu.
PMID: 32963283 DOI: 10.1038/s42003-020-01246-z
Abstract

The omentum is the most common site of ovarian Cancer metastasis. Immune cell clusters called milky spots are found throughout the omentum. It is however unknown if these immune cells contribute to ovarian Cancer metastasis. Here we report that omental macrophages promote the migration and colonization of ovarian Cancer cells to the omentum through the secretion of chemokine ligands that interact with Chemokine Receptor 1 (CCR1). We found that depletion of macrophages reduces ovarian Cancer colonization of the omentum. RNA-sequencing of macrophages isolated from mouse omentum and mesenteric adipose tissue revealed a specific enrichment of chemokine ligand CCL6 in omental macrophages. CCL6 and the human homolog CCL23 were both necessary and sufficient to promote ovarian Cancer migration by activating ERK1/2 and PI3K pathways. Importantly, inhibition of CCR1 reduced ovarian Cancer colonization. These findings demonstrate a critical mechanism of omental macrophage induced colonization by ovarian Cancer cells via CCR1 signaling.

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