Selection of metastatic breast cancer cells based on adaptability of their metabolic state.

PloS One
Balraj SinghAnthony Lucci

Abstract

A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind) variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemo...Continue Reading

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Citations

Sep 27, 2015·Neoplasia : an International Journal for Oncology Research·Rui V SimõesEllen Ackerstaff
Sep 4, 2013·The Journal of Clinical Investigation·Christopher T HensleyRalph J DeBerardinis
Jun 9, 2020·The Journal of Experimental Medicine·Maria Victoria RecouvreuxCosimo Commisso

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