Prevention and management of metastasis has become a major focus and challenge in breast cancer patients. The reprogramming of energy metabolism in tumour cells has long been recognised but only recently has it been elevated to the status of a hallmark of cancer1. In this study, we used MDA-MB-231HM cells, a high metastatic variant of MDA-MB-231 cells derived from six cycles of pulmonary metastasis to the mammary fat pad 2 to investigate the phenotypic differences, as well as differences in energy metabolism pathways between the highly metastatic cells and the parental cell line.
MDA-MB-231 HMln5 (HM) cells were isolated from an axillary lymph node metastasis from Balb-SCID mice imfp inoculated with MDA-MB-231 HM cells and reference 231 HM cells (Cancer Metastasis Laboratory, Peter MacCallum Cancer Centre). To explore the phenotypic differences between the HM cells and parent MDA-MB-231 (NI) cells, we compared levels of serum-induced proliferation by cell enumeration and paclitaxel-induced cytotoxicity. Glycolytic and oxidative pathways were examined using the XF Analyzer (Seahorse Bioscience) and by measuring expression of enzymes in glycolysis and tricarboxylic acid cycle (TCA) pathways by qRT-PCR.
HM and NI cells showed similar levels of basal proliferation, whereas serum induced greater responses in the NI cells. Compared to the NI cells, the HM cells were more resistant to Paclitaxel-induced cytotoxicity. The HM cells exhibited significantly higher basal mitochondrial respiration and glycolysis; and showed increase expression of enzymes in glycolysis pathways as well as those of the TCA cycle.
Cells that have gone through cycles of metastasis and re-implantation became more metabolically active compared to the parent lines. We are currently examining other contrasts between the phenotypes of these cell lines.