Metabolic differences between primary and brain metastatic breast tumors revealed by in vivo [U-¹³C]-glucose infusion in mice

Metastatic breast tumors must adapt to the metabolic constraints of their target tissues. To understand how tumor metabolism varies across sites, we compared glucose utilization in primary mammary fat pad (MFP) tumors and brain metastases derived from the breast cancer cell line MDA-MB-231. Tumors in each site displayed distinct patterns of metabolite labeling, reflecting differences in nutrient availability and biosynthetic activity. Brain tumors exhibited higher labeling of amino acids and TCA cycle intermediates, consistent with increased synthesis to overcome restricted nutrient access in the brain, whereas MFP tumors showed greater nucleotide synthesis activity. These findings illustrate how the tumor microenvironment shapes metabolic adaptation and highlight the flexible strategies cancer cells use to maintain growth in diverse tissues.