posters International Association for Breast Cancer Research 2014

An MDA-MB-231 cell line derived from lymph node metastasis has lower proliferation but higher metabolism (#112)

Yan Tu 1 , Ebony Fietz 2 , James Ryall 2 , Cameron N Johnstone 3 , Alastair Stewart 1
  1. Department of Pharmacology, University of Melbourne, Parkville, VIC, Australia
  2. Department of Physiology, University of Melbourne, Parkville, VIC, Australia
  3. Cancer Metastasis Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia

Prevention and management of metastasis has become a major focus and challenge in managing breast cancer. 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 cancer (Hanahan et al., 2011). However, the specific metabolic signature that associates with increased metastatic behaviour in breast cancer cells is not well understood.

In this study, we used the MDA-MB-231HM.LNm5 cell line, a highly metastatic variant of the MDA-MB-231 cell line derived from six cycles of pulmonary metastasis from the mammary fat pad (Li et al., 2006), to investigate phenotypic differences, such as migration and proliferation, as well as differences in energy metabolism pathways between the highly metastatic and the parental cell lines.

MDA-MB-231HM.LNm5 cells were isolated from an axillary lymph node metastasis from NSG mice inoculated in a mammary fat pad with MDA-MB-231HM cells (Cancer Metastasis Laboratory, Peter MacCallum Cancer Centre). Compared to parental MDA-MB-231 cells, the MDA-MB-231HM.LNm5 cell line shows increased migration in the presence of FCS (1%v/v) in a modified Boyden assay (167±26% P<0.05). In contrast, proliferation after 48h was significantly lower (59±8% P<0.05). Moreover, MDA-MB-231HM.LNm5 cells were less sensitive to Paclitaxel-induced (1μM) cytotoxicity than the parental MDA-MB-231 cells (28±3% vs. 47±8%, P<0.05). The rates of oxygen consumption (OCR) and extracellular acidification (ECAR), which are proportional to mitochondrial respiration and glycolysis respectively, were examined using the XF Analyser (Seahorse Bioscience).  MDA-MB-231HM.LNm5 cells showed significantly higher basal mitochondrial respiration, ATP production and non-mitochondrial respiration (P<0.05).

Our results demonstrate that MDA-MB-231 cells that have gone through serial in vivo passaging become more migratory, more metabolically active but less proliferative. These observations support the view that reduced proliferation may be important for the survival of already disseminated cancer cells.

  1. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell 144(5): 646-674.
  2. Li DQ, Wang L, Fei F, Hou YF, Luo JM, Wei C, et al. (2006). Identification of breast cancer metastasis-associated proteins in an isogenic tumor metastasis model using two-dimensional gel electrophoresis and liquid chromatography-ion trap-mass spectrometry. Proteomics 6(11): 3352-3368.