Isothermal Microcalorimetry of Tumor Cells: Enhanced Thermogenesis by Metastatic Cells

Abstract

Tumor cells exhibit rewired metabolism. We carried out comparative analyses attempting to investigate whether metabolic reprograming could be measured by isothermal microcalorimetry. Intact metastatic cell lines of tongue cell carcinoma, human and murine melanoma, lung, and breast tumors consistently released more heat than nonmetastatic cells or cells displaying lower metastatic potential. In tongue squamous carcinoma cells mitochondrial enriched extract reproduced the heat release pattern of intact cells. Cytochalasin D, an actin filament inhibitor, and suppression of metastasis marker Melanoma associated gene 10 (MAGEA10) decreased heat release. Uncoupling protein 2 was highly expressed in metastatic cells, but not in non-metastatic cells. Carnitine palmitoyl transferase-1 inhibitor, Etomoxir strongly inhibited heat release by metastatic cells, thus linking lipid metabolism to thermogenesis. We propose that heat release may be a quantifiable trait of the metastatic process.

Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis

“…Tumor cells for example exhibit a significantly different and elevated metabolism from that of other cells. Changes in lipid metabolism have been linked with changes of the thermogenic profile [ 12 ]. Thermogenesis can be measured by isothermal microcalorimetry.…”

“…It has been suggested that metastatic cells utilize metabolic pathways that supply extra energy to enable increased motility and invasiveness [ 12 ]. For example, Lemos et al described an increased heat release exclusively in metastatic cell lines of different origins (human oral squamous cell carcinoma, melanoma, non-small-cell lung and breast cancer, and murine melanoma cells) [ 12 ]. They investigated the influence of MAGEA10 protein on this process.…”

“…They further investigated the influence of uncoupling proteins, mainly UCP, and suggested a possible mitochondrial contribution in metastatic cell thermogenesis by enhancing thermogenesis through mitochondrial uncoupling. There is little known about the mechanisms of this, but one explanation for higher thermogenesis of migrating tumor cells might result from an increased channeling of ATP from fatty acid oxidation [ 12 ].…”

“…In this context, it has been proposed that metastatic cells have an enhanced thermogenesis. This was experimentally demonstrated for different cell lines with variations of metastatic potential including tongue squamous cell carcinoma, human non-small-cell lung carcinoma, human breast adeno carcinoma and murine melanoma [ 12 ]. However, primary and metastatic cells in these experiments did not originate from the same host.…”

“…However, primary and metastatic cells in these experiments did not originate from the same host. Experiments of these previous publications on the relationships of thermogenesis or adhesion strength to the metastatic potential of tumor cells used either cell lines of the same tumor entity but from different patients or artificial, metastatic subclones of the original cell line [ 10 , 12 ].…”