Abstract 3407: Human omental-derived adipose stem cells support growth of intra-peritoneal ovarian cancer xenografts and increase in-vitro proliferation and migration of ovarian cancer cells
Authors: Sharp Hadley , Marini Frank , Solley Travis , Broaddus Russell , Kolonin Mikhail , Mok Sam , Schmandt Rosemarie , Woodward Wendy , Andreef Michael , Lu Karen , Klopp Ann 
Published: June 2012

Introduction: Adipose tissue retains a population of multipotent mesenchymal stromal cells (ASC) which exhibit tumor tropism, similar to bone marrow derived mesenchymal stem cells (MSC); both augment tumor initiation, growth and metastasis. Excess visceral adipose tissue increases the risk of ovarian cancer and the omentum is a frequent site of ovarian cancer metastasis. We hypothesize omentum is a source of ASC which promote ovarian cancer progression.

Methods: ASC were isolated from the omentum (O-ASC) of 5 patients with endometrial or ovarian cancer (1-3: early stage/low grade, 4 and 5: IIIC serous ovarian). O-ASC were characterized with flow cytometry and multi-lineage differentiation assays. Luciferase-labeled ovarian cancer cell lines (OVCA433 and OVCA429) were co-cultured with O-ASC and tumor cell proliferation was quantitated using luciferase imaging. Transwell migration assays were performed with OVCA433 and OVCA429 with conditioned media from OSC, MSC, and subcutaneous adipose derived ASC. 9 female NOD.CB17-Prkdc SCID/j mice (age 14 weeks) received: (1) Intraperitoneal (IP) injection of luciferase labeled SCOV3 human ovarian cancer cells or (2) IP injection of luciferase labeled SCOV3 human ovarian cancer cells mixed directly with RFP-labeled hOSC on day 1 and 28. Tumor burden was measured with luciferase imaging and magnetic resonance imaging.

Results: O-ASC exhibited mesenchymal morphology, cell surface marker expression similar to MSC (CD45, 0.4%; CD 90, 84.6%;CD44,77.8%;CD 105, 38.5%), osteogenic and adipogenic differentiation. OVCA433 proliferation was significantly increased when co-cultured with O-ASC as compared to control, with a non-significant increase in OVCA429 proliferation observed (average luminescence of 1348.4 vs. 2558.6 p&lt;0.01, 3094.2 vs. 2298.6 p = 0.19 respectively). Migration of OVCA433 was significantly increased compared to tumor cells alone for all 5 OSC lines and MSC line (average absorbance reflecting number of migrated cells 0.15, 0.29. 0.32, 0.45, 0.56 for OSC1-5 and 0.50 MSC respectively, p&lt;0.05 in all cases). Similar trends were seen with OVCA429, with an increase in ovarian cancer cell migration relative to controls in O-ASC 2-5 and MSC. Media from O-ASC 4 and 5, derived from patients with stage III serous ovarian cancer, had the most potent effects on in-vitro migration of OVCA429 and 433 cells. Of the mice bearing IP SKOV3 ovarian tumors, those receiving O-ASC on day 1 and 28 developed larger tumor burden (mean photons/cm2 on day 32 of 1.1 × 107 vs 6.0 × 107, p=0.04).

Conclusions: ASC from the omentum can promote proliferation and migration of ovarian cancers. Future studies will determine if patients with advanced cancers have functionally distinct adipose stem cells due to exposure to tumor secreted factors or inherent underlying differences in normal tissue biology.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3407. doi:10.1158/1538-7445.AM2011-3407