title: Milky spots promote ovarian cancer metastatic colonization of peritoneal adipose in experimental models.
abstract: The goal of controlling ovarian cancer metastasis formation has elicited considerable interest in identifying the tissue microenvironments involved in cancer cell colonization of the omentum. Omental adipose is a site of prodigious metastasis in both ovarian cancer models and clinical disease. This tissue is unusual for its milky spots, comprised of immune cells, stromal cells, and structural elements surrounding glomerulus-like capillary beds. The present study shows the novel finding that milky spots and adipocytes play distinct and complementary roles in omental metastatic colonization. In vivo assays showed that ID8, CaOV3, HeyA8, and SKOV3ip.1 cancer cells preferentially lodge and grow within omental and splenoportal fat, which contain milky spots, rather than in peritoneal fat depots. Similarly, medium conditioned by milky spot-containing adipose tissue caused 75% more cell migration than did medium conditioned by milky spot-deficient adipose. Studies with immunodeficient mice showed that the mouse genetic background does not alter omental milky spot number and size, nor does it affect ovarian cancer colonization. Finally, consistent with the role of lipids as an energy source for cancer cell growth, in vivo time-course studies revealed an inverse relationship between metastatic burden and omental adipocyte content. Our findings support a two-step model in which both milky spots and adipose have specific roles in colonization of the omentum by ovarian cancer cells.
authors.affiliation: Department of Pathology-Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Clark
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
authors.forename: Michael
authors.initials: M
authors.lastname: Schoof
authors.forename: Irving
authors.initials: I
authors.lastname: Rodriguez
authors.forename: Betty
authors.initials: B
authors.lastname: Theriault
authors.forename: Marina
authors.initials: M
authors.lastname: Chekmareva
authors.forename: Carrie
authors.initials: C
authors.lastname: Rinker-Schaeffer
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D001399:Azure Stains; D045744:Cell Line, Tumor; D004396:Coloring Agents; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D009852:Omentum / Q000473:pathology*; D010051:Ovarian Neoplasms; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary*; D020858:Tissue and Organ Harvesting
chemical_list: D001399:Azure Stains; D004396:Coloring Agents