title: In Vivo and Ex Vivo Approaches to Study Ovarian Cancer Metastatic Colonization of Milky Spot Structures in Peritoneal Adipose.
abstract: High-grade serous ovarian cancer (HGSC), the cause of widespread peritoneal metastases, continues to have an extremely poor prognosis; fewer than 30% of women are alive 5 years after diagnosis. The omentum is a preferred site of HGSC metastasis formation. Despite the clinical importance of this microenvironment, the contribution of omental adipose tissue to ovarian cancer progression remains understudied. Omental adipose is unusual in that it contains structures known as milky spots, which are comprised of B, T, and NK cells, macrophages, and progenitor cells surrounding dense nests of vasculature. Milky spots play a key role in the physiologic functions of the omentum, which are required for peritoneal homeostasis. We have shown that milky spots also promote ovarian cancer metastatic colonization of peritoneal adipose, a key step in the development of peritoneal metastases. Here we describe the approaches we developed to evaluate and quantify milky spots in peritoneal adipose and study their functional contribution to ovarian cancer cell metastatic colonization of omental tissues both in vivo and ex vivo. These approaches are generalizable to additional mouse models and cell lines, thus enabling the study of ovarian cancer metastasis formation from initial localization of cells to milky spot structures to the development of widespread peritoneal metastases.
authors.affiliation: Section of Urology, Department of Surgery, The University of Chicago.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
authors.affiliation: Section of Urology, Department of Surgery, The University of Chicago.
authors.forename: Robert
authors.initials: R
authors.lastname: Clark
authors.affiliation: Department of Pathology, Robert Wood Johnson Medical School.
authors.forename: Marina
authors.initials: M
authors.lastname: Chekmareva
authors.affiliation: Section of Urology, Department of Surgery, The University of Chicago.
authors.forename: Amy
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network.
authors.forename: Sophia
authors.initials: S
authors.lastname: George
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University of Toronto, University Health Network.
authors.forename: Patricia
authors.initials: P
authors.lastname: Shaw
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University of Toronto, University Health Network; Departments of Medicine, Pharmacology, and Cancer Biology, Duke University Medical Center.
authors.forename: Victoria
authors.initials: V
authors.lastname: Seewaldt
authors.affiliation: Section of Urology, Department of Surgery, The University of Chicago; crinkers@uchicago.edu.
authors.forename: Carrie
authors.initials: C
authors.lastname: Rinker-Schaeffer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D018205:Neoplasms, Adipose Tissue / Q000556:secondary*; D009852:Omentum / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000556:secondary*; D013234:Stem Cells