Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis

Abstract

Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.

Perfusion-Based Bioreactor Culture and Isothermal Microcalorimetry for Preclinical Drug Testing with the Carbonic Anhydrase Inhibitor SLC-0111 in Patient-Derived Neuroblastoma

“…We have previously demonstrated the effectiveness of evaluating novel therapeutic approaches in rare childhood tumors using isothermal microcalorimetry of organotypic slice cultures [ 19 ]. More recently, we have been able to link a higher metastatic potential of tumor cells to biophysical properties, such as decreased adherence and increased thermogenesis [ 54 ]. Isothermal microcalorimetry can also be of advantage in evaluating thermogenesis of neuroblastoma cells under stimulation with different nutrient supplies [ 55 ].…”

Increased Proliferation of Neuroblastoma Cells under Fructose Metabolism Can Be Measured by Isothermal Microcalorimetry

“…Thermogenesis can highly sensitively be measured by isothermal microcalorimetry of cancer cells [ 4 ]. It can be detected in the range of microwatts under isothermal conditions [ 8 ].…”

“…Moreover, we recently published a manuscript describing a higher thermogenic profile for metastatic tumor cells in matching cell lines originating from metastatic lymph nodes compared to primary tumor of the same patient. Metastatic cells were less adhesive compared with primary tumor cells [ 4 ]. Our present results show that isothermal microcalorimetry is a sensitive method to detect slight changes in tumor cell thermogenesis, which can be the result of cellular changes in tumor cells metabolism through stimulation with glucose or fructose, as in our case, or of otherwise induced changes of cell properties.…”

“…They can, for example, adapt to hypoxia by transforming their phenotype to a more hypoxia-resistant and often aggressive one. We have previously shown that metastatic cell lines exhibit a higher thermogenic profile than primary tumor cell lines that were derived from the same patient [ 4 ]. Furthermore, we were able to evaluate treatment response of patient-derived tumor slice cultures to inhibition of hypoxia-dependent targets by monitoring thermogenic changes [ 5 ].…”

Titrating Avidity of Yeast-Displayed Proteins Using a Transcriptional Regulator

“…The cells on the disk underwent a spinning program consisting of a 20 s acceleration ramp, a 5 min constant spinning at the indicated angular velocity (rpm), and a 20 s deceleration in a TBS–Ca 2+ buffer chamber. Image analysis and data treatment were performed as described elsewhere . Detachment profiles for n = 3 technical replicates were plotted and fitted using a global sigmoid probabilistic model to extract the shear stress value (τ 50 ), at which 50% of the cells remained adherent .…”