Extended Data Fig. 9 |. TCA and glucose use flux measurement in primary breast cancer xenograft tumours and their spontaneous lung metastases.

(a) Volume of breast cancer xenograft primary tumours (n = 12 mice MDA-MB-231-LM2, n = 10 mice Sum159-M1a). (b) Weight of mouse lungs, either in non-tumour-bearing mice or mice with metastases seeded from primary breast cancer xenograft tumours (n = 6 mice no tumour, n = 11 mice Sum159-M1a, n = 2 mice MDA-MB-231-LM2). (c) Luciferase imaging showing metastases in lungs of mice with primary breast cancer xenograft tumours, n = 1 mouse per tumour type shown. (d) [1-¹³C] 2-deoxyglucose-phosphate concentration after 15 min [1-¹³C] 2-deoxyglucose infusion in primary breast xenograft tumours, and lungs with metastases from the same mice (n = 2 mice for MDA-MB-231-LM2 tumour and lung, n = 3 for Sum159-M1a tumour and lung). (e) Glucose use fluxes of primary tumour and lung from mice with MD-MBA-231-LM2 breast xenograft tumours, n = 2 mice per tissue. (f) Glucose use fluxes of primary tumour and lung from mice with Sum159-M1A breast xenograft tumours, n = 3 mice per tissue, p-value from two-tailed t test. (g) TCA metabolite m+2 and m+1 labelling from [U-¹³C] lactate primed infusion (points) and model fits (lines) in primary tumours and lungs of mice with MDA-MB-231-LM2 tumours, n = 6 mice per tissue. (h) Hematoxylin and eosin staining of lung from mouse with MDA-MB-231-LM2 primary tumour; arrows indicate metastatic nodules. (i) Glutamate m+2 labelling intensity after 10 min [U-¹³C] lactate primed infusion, same lung as in (h), arrows indicate metastatic nodules. (j) Glutamate m+2 labelling intensity from healthy and metastatic regions of lungs with MDA-MB-LM2 metastases, n = 3 mice, paired t-test. (k) Protein abundance of detected human mitochondrial oxidative-phosphorylation proteins in MDA-MB-231-LM2 primary tumours and lungs bearing metastases from the same mice, all values normalized to the median value of that protein in the primary tumour, n = 7 per sample type. All error bars show mean +/− standard deviation.