Abstract 1492: Eavesdropping of crosstalk between adipose stem cells (ASC) and ovarian cancer cells
Authors: Aleksandra K. Nowicka, Travis Solley, Hadley J. Sharp, Frank C. Marini, Russell Broaddus, Mikhail Kolonin, Samuel Mok, Wendy Woodward, Karen H. Lu, Ann H. Klopp
Journal: Cancer Research (2012)

Abstract Background Adipose tissue contains a population of multipotent adipose stromal cells (ASC) which migrate into tumors and form supportive tumor stroma elements. ASCs release various growth factors, cytokines and metabolites that influence on physiochemical nature of the local environment. Ovarian cancer cells have a predilection for metastasis in omentum, the primary repository for visceral adipose. The effects of omental derived adipose stem cells (O-ASC) and subcutaneous tissue derived adipose stem cells (SC-ASC) on ovarian cancer biology including ovarian cancer proliferation, gene expression and response to chemotherapy were investigated. Methods and Results Luciferase labelled ovarian carcinoma cells (OVCA 429) were co-cultured with O-ASC, SC-ASC and control fibroblast line Wi38. Significantly higher levels of luciferase activity was detected when ovarian carcinoma cells were co-cultured with O-ASC than with SC-ASC and Wi38 (3470.4 RLU vs 1253.2 RLU, p=&amp;lt;0.005). Moreover, co-culture of 429 cells with ASCs in presence of different concentrations of Taxol revealed that O-ASC influence tumor cell chemosensitivity. Additionally, O-ASC promoted formation of significantly more ovarian carcinoma tumorispheres which were more closer associated to each other than those created in sphere medium only. To identify differentially expressed genes in O-ASC and SC-ASC, we performed microarray experiments (NimbleGen platform) which were analyzed using Ingenuity Pathway Analysis (IPA) software. The highest expressed genes were connected with growth, proliferation and development of cells and most of the proteins coded by these genes were localized in the extracellular space, plasma membrane or exosomes (CALR, UNC5B in O-ASC or COL1A2, FN1 in SC-ASC). We also performed ELISA assays focused on release of growth factors which revealed that O-ASC and SC-ASC secrete more VEGF (1678 pg/ml) and FGF (29 pg/ml) compared to control cells Wi38 (114 pg/ml and 2.7 pg/ml respectively). Chemokine SDF-1α was also secreted in high level by O-ASC S1 (1537 pg/ml) but SC-ASC released only 187 pg/ml relative to Wi38 (706 pg/ml) which indicates that these two types of adipose stem cells can create different surrounding environment. Summary O-ASC cells have unique tumor promoting effects and create specific environmental niche by releasing growth factors, cytokines and other factors which can stimulate ovarian cancer cells to grow faster and clump together. ASC may also influence protection of ovarian cancer from toxicity of chemotherapeutics. The knowledge about microenvironmental crosstalk between normal stem cells and tumor cells can contribute in the development of new treatment to prevent metastasis of ovarian cancer and make them vulnerable to chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1492. doi:1538-7445.AM2012-1492