title: New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination.
abstract: Emerging evidence suggest that many high-grade serous "ovarian" cancers (HGSOC) start in the fallopian tube. Cancer cells are then recruited to the ovary and then spread diffusely through the abdomen. The mechanism of ovarian cancer spread was thought to be largely due to direct shedding of tumor cells into the peritoneal cavity with vascular spread being of limited importance. Recent work challenges this dogma, suggesting hematogenous spread of ovarian cancer may play a larger role in ovarian cancer cell metastasis than previously thought. One reason the role of vascular spread of ovarian cancer has not been fully elucidated is the lack of easily accessible models of vascular ovarian cancer metastasis. Here, we present 3 metastatic models of ovarian cancer which confirm the ability of ovarian cancer to hematogenously spread. Strikingly, we observe a high rate of metastasis to the ovary with the development of ascites in these models. Interestingly, oophorectomy resulted in a complete loss of peritoneal metastases and ascites. Taken together, our data indicate that hematogenously disseminated HGSOC cells have a unique tropism for the ovary and that hematogenous spread in ovarian cancer may be more common than appreciated. Furthermore, our studies support a critical role for the ovary in promoting HGSOC cell metastasis to the abdomen. The models developed here represent important new tools to evaluate both the mechanism of cancer cell recruitment to the ovary and understand and target key steps in ovarian cancer metastasis.
authors.affiliation: Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA. Electronic address: coffmanl@med.umich.edu.
authors.forename: Lan G
authors.initials: LG
authors.lastname: Coffman
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Burgos-Ojeda
authors.affiliation: Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cho
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Shoumei
authors.initials: S
authors.lastname: Bai
authors.affiliation: Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Buckanovich
mesh_terms: D000005:Abdomen / Q000473:pathology*; D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000473:pathology / Q000556:secondary*; D010052:Ovariectomy; D010053:Ovary / Q000473:pathology*