Delineating metabolic signatures of head and neck squamous cell carcinoma: Phospholipase A2, a potential therapeutic target

Abstract

A better understanding of molecular pathways involved in malignant transformation of head and neck squamous cell carcinoma (HNSCC) is essential for the development of novel and efficient anti-cancer drugs. To delineate the global metabolism of HNSCC, we report 1H NMR-based metabolic profiling of HNSCC cells from five different patients that were derived from various sites of the upper aerodigestive tract, including the floor of mouth, tongue and larynx. Primary cultures of normal human oral keratinocytes (NHOK) from three different donors were used for comparison. 1H NMR spectra of polar and non-polar extracts of cells were used to identify more than thirty-five metabolites. Principal component analysis performed on the NMR data revealed a clear classification of NHOK and HNSCC cells. HNSCC cells exhibited significantly altered levels of various metabolites that clearly revealed dysregulation in multiple metabolic events, including Warburg effect, oxidative phosphorylation, energy metabolism, TCA cycle anaplerotic flux, glutaminolysis, hexosamine pathway, osmo-regulatory and anti-oxidant mechanism. In addition, significant alterations in the ratios of phosphatidylcholine/lysophosphatidylcholine and phosphocholine/glycerophosphocholine, and elevated arachidonic acid observed in HNSCC cells reveal an altered membrane choline phospholipid metabolism (MCPM). Furthermore, significantly increased activity of phospholipase A2 (PLA2), particularly cytosolic PLA2 (cPLA2) observed in all the HNSCC cells confirm an altered MCPM. In summary, the metabolomic findings presented here can be useful to further elucidate the biological aspects that lead to HNSCC, and also provide a rational basis for monitoring molecular mechanisms in response to chemotherapy. Moreover, cPLA2 may serve as a potential therapeutic target for anti-cancer therapy of HNSCC.

Thyroid cancer metabolism: A review

“…These transporters couple cancer cells so that hypoxic cells maintain functioning glycolytic metabolism while aerobic tumor cells recycle and utilize lactate and other high-energy substrates produced by them [13]. It is believed that cells with decreased lactate levels have high lactate uptake via MCTs, allowing them to generate large amounts of ATP via OXPHOS [25,26]. These transporters may represent possible therapeutic targets.…”

Energy Metabolism in a Matched Model of Radiation Resistance for Head and Neck Squamous Cell Cancer

“…Previous investigations of HNSCC metabolism have revealed dysregulation of multiple metabolic pathways such as OXPHOS, TCA cycle and glutaminolysis (19), as well as a general reliance on glucose as the dominant energy source for survival and proliferation (17). However, to our knowledge, the metabolic changes associated with radiation-resistant tumor cells in HNSCC have not been investigated.…”

1H NMR metabolic profiling of human serum associated with benign and malignant gallstone diseases

“…Spectral alignment was checked prior to statistical analysis. Serum NMR spectra showed no need of alignment as there was no peak shifting in any part of spectra (MacKinnon et al 2012). Spectral region between 0.5 and 9.0 ppm were exported to Microsoft office Excel 2007 (Microsoft Corporation, USA) after mean centering and normalization.…”

“…The HRMAS studies on different cancerous tissues including breast (Whitehead and KieberEmmons 2005;Sitter et al 2002Sitter et al , 2006, oral squamous cells (Srivastava et al 2011), prostrate (Stenman et al 2011;Stenman et al 2010;Van Asten et al 2008;MacKinnon et al 2012b), colorectal (Chan et al 2009;Seierstad et al 2008), kidneys (Tate et al 2000;Waters et al 2000), colon (Righi et al 2009), brain tissues (Righi et al 2009;Wright et al 2010;Cheng et al 2000), hepatocellular carcinoma (Yang et al 2007), lungs (Rocha et al 2009), cervical cancers (Sitter et al 2004;Lyng et al 2007), ovarian epithelial (Ben Sellem et al 2011), head and neck squamous cells (Somashekar et al 2011;Tripathi et al 2012), gallbladder cancer (Bharti, et al 2012a) etc. have provided very new insights into the prognosis of cancers along with some potential biomarkers for detection.…”