Abstract 3613: Opposite effects of adipocytes and adenosine on hematological cancer cell survival and proliferation in vitro

Abstract

Abstract Background: Tumor microenvironment is composed of stroma that contains adipocytes. It is well established that obesity is a cancer risk factor and is associated with a poor prognosis in cancer patients. Cancer-associated adipocytes are thought to interact with cancer cells to promote tumor progression. Moreover, adipocytes express CD73 and can produce adenosine which also has been shown to promote cancer development through its interaction with adenosine receptors on solid cancer cells. As hematological malignancies can proliferate in bone marrow which is rich in adipocytes, we hypothesized that these latter could influence cancer cell survival and proliferation through the action of adenosine. Methods: CD73 enzymatic activity was determined on human pre-adipocyte cells (hMAD, ASC) by the Malachite Green Assay. The expression of adenosine receptor was assessed on human T-acute lymphoblastic leukemia cells (Jurkat) and follicular lymphoma cells (RL) by FACS analysis. Cancer cell proliferation and percentage of cell death were evaluated by FACS using CFSE staining and DAPI respectively. Survival and proliferation was evaluated in the absence or presence of human pre-adipocytes (hMAD, ASC) or adenosine with or without an adenosine deaminase inhibitor (deoxycoformycin 10 µM). Results: CD73 enzymatic activity was observed both in hMAD and ASC cells, while Jurkat and RL cells express the four adenosine receptors A1, A2A, A2B and A3. Hematological cancer cells tend to proliferate more when co-cultivated with pre-adipocytes (Jurkat 63,8% alone vs 69,2% with hMAD; RL 67,7% alone vs 73,9% with hMAD; Jurkat 62,4% alone vs 69,6% with ASC; RL 66,1% alone vs 74,8% with ASC). These cells also tend to have a lower rate of spontaneous cell death in same conditions (Jurkat 31,4% alone vs 23,6% with hMAD; RL 37,1% alone vs 30,1% with hMAD; Jurkat 32,7% alone vs 30,9% with ASC; RL 53,5% alone vs 36,0% with ASC). In contrast, we found that hematological cancer cells proliferate less in the presence of adenosine in a dose-dependent manner starting from 200 µM in media containing 1% serum (Jurkat 71,0% alone vs 68,6% with 200 µM adenosine and 47,6% with 200 µM adenosine + deoxycoformycin; RL 79,0% alone vs 73,3% with 200 µM adenosine and 59,8% with 200 µM adenosine + deoxycoformycin). Finally, adenosine also induced more cell death in these cells (Jurkat 28,6% alone vs 41,2% with 200 µM adenosine and 57,4% with 200 µM adenosine + deoxycoformycin; RL: 28,2% alone vs 47,9% with 200 µM adenosine + deoxycoformycin). Conclusion: Adipose cells have pro-proliferative and protective effects on hematological cancer cells in vitro while acute exposure to adenosine at supraphysiological concentrations has a cytotoxic effect. These results do not suggest that adipocytes favor proliferation through adenosine signaling. Citation Format: Cécile Bossard, Charles Dumontet, Lars P. Jordheim. Opposite effects of adipocytes and adenosine on hematological cancer cell survival and proliferation in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3613. doi:10.1158/1538-7445.AM2014-3613