Differential expression of cytokines and receptor expression during anoxic growth

Abstract

ObjectiveCell density in tumor cell three dimensional (3D) cultures affects secretome expression of components. A microenvironment characteristic shared by high-density 3D cell culture and in vivo tumor masses is poor oxygenation, with anoxia being a natural cell state in tumor centers. Until recently, the ability to study anoxia-adapted cell physiology was not possible. Using a newly-developed methodology, anoxic HeLa cell secretome expression was measured.ResultsAnoxic HeLa cell cytokine levels after 3 days’ (hypoxia inducible factor, HIF1 positive) and 10 days’ growth (HIF1 negative; anaerobic respiration) were significantly (p < 0.01) higher than normoxic controls for: IL-8 (1.8- and 3.4-fold higher, respectively), GRO (1.3- and 1.1-fold higher, respectively), and IL-11 (1.4- and 1.1-fold higher, respectively). In contrast, G-CSF, IFNα2, and CXCL-10 levels decreased over time (day 3 vs. day 10). Thus, metabolically active HeLa cells respond to the lack of oxygen, in part, by regulating the levels of cytokines produced. Cytokines expressed at increased levels, in the absence of oxygen, correspond to a secretomic profile reported for paracrine signaling pathways associated with metastasis. Further studies defining physiologic changes that occur upon anoxic growth may lead to the discovery of novel chemotherapeutic drug targets.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3520-5) contains supplementary material, which is available to authorized users.

The Pharmacological Effects of Spatholobi Caulis Tannin in Cervical Cancer and Its Precise Therapeutic Effect on Related circRNA

“…The human cervical carcinoma cell line HeLa was obtained from the Chinese Academy of Sciences (Shanghai, China). DMEM (RPMI DMEM, Gibco, Grand Island, NY, USA) containing 10% fetal calf serum (FCS, Gibco) was used to culture the cells at 5% CO 2 , 100% humidity, and 37°C (Nuaire, USA) 38 …”

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

“…The effect of hypoxia on the expressions of CXCL1 and CXCL2 depends on the type of cancer. For example, chronic hypoxia does not affect the expression of either chemokine in lung adenocarcinoma [ 154 ] but does increase the expression of CXCL1 in human acute myeloid leukemia cells [ 155 ], cervical cancer cells [ 156 ] and hepatocarcinoma cells [ 157 ]. The expressions of both CXCL1 and CXCL2 are increased by chronic hypoxia in PC-3 prostate cancer cells [ 14 ] but reduced in SK-OV-3 ovarian adenocarcinoma and WM793B melanoma cells.…”

“…Chronic hypoxia also increases the expression of CXCL10 in HepG2 cells (hepatocellular carcinoma) [ 216 ]. On the other hand, studies on cancer cells such as HeLa cells (cervical cancer) [ 156 ], 9L glioma cells (brain tumor) [ 217 ], breast cancer cells [ 175 , 177 ], ovarian cancer cells, colon cancer cells and lung cancer cells [ 175 ] show that chronic hypoxia reduces the expression of CXCL10, as in studies on noncancer cells such as primary hepatocytes [ 178 ] and rabbit alveolar macrophages [ 201 ]. This effect may depend on HIF-1 or on the reduction in transcriptional NF-κB activity [ 218 ].…”

Putative pathways fueling anaerobic mitochondrial respiration

“…We pioneered a system for the study of anaerobic cell physiology and the resultant oxygentriggered metabolic rewiring. In this model system, both cancerous and noncancerous cell lines retained viability for over 2 weeks (maximum time tested), replicated, and autophagy was suppressed [21,22]. In addition, HIF expression cycled on and off in response to cellular release of ROS.…”

“…In addition, HIF expression cycled on and off in response to cellular release of ROS. In vitro support of the role anaerobic rewiring may play in tumorigenesis is the finding that HeLa cells grown anaerobically shift their cytokine secretome expression to one that is pro-angiogenic [22]. Thus, characterization of anaerobic cell physiology is essential, particularly since in addition to mucosal surfaces, stem cell niches and solid tumors contain anaerobic areas [23][24][25].…”