Epithelial and mesenchymal tumor compartments exhibit in vivo complementary patterns of vascular perfusion and glucose metabolism.
Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of "mesenchymalization" such as desmoplasia or epithelial-mesenchymal transition.
Galiè
Mirco
M
Dipartimento Scienze Morfologico-Biomediche, sez. Anatomia ed Istologia, Università di Verona, Verona, Italy. mirco@anatomy.univr.it
Farace
Paolo
P
Nanni
Cristina
C
Spinelli
Antonello
A
Nicolato
Elena
E
Boschi
Federico
F
Magnani
Paolo
P
Trespidi
Silvia
S
Ambrosini
Valentina
V
Fanti
Stefano
S
Merigo
Flavia
F
Osculati
Francesco
F
Marzola
Pasquina
P
Sbarbati
Andrea
A
D000818:Animals; D002277:Carcinoma / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D019786:Gadolinium DTPA; D005947:Glucose / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D049268:Positron-Emission Tomography; D051381:Rats
D019788:Fluorodeoxyglucose F18; D005947:Glucose; D019786:Gadolinium DTPA