Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts.
Several studies have linked vascular density, identified in histologic sections, to "metastatic risk." Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if human breast and prostate cancer xenografts preselected for differences in invasive and metastatic characteristics established correspondingly different vascular volume and permeability, quantified here with noninvasive MRI of the intravascular contrast agent albumin-GdDTPA. Tumor vascular volume and permeability of human breast and prostate cancer xenografts were characterized using MRI. Parallel studies confirmed the invasive behavior of these cell lines. Vascular endothelial growth factor (VEGF) expression in the cell lines was measured using ELISA and Western blots. Metastasis to the lungs was evaluated with spontaneous as well as experimental assay. Metastatic tumors formed vasculature with significantly higher permeability or vascular volume (P<.05, two-sided unpaired t test). The permeability profile matched VEGF expression. Within tumors, regions of high vascular volume usually exhibited low permeability whereas regions of low vascular volume exhibited high permeability. We observed that although invasion was necessary, without adequate vascularization it was not sufficient for metastasis to occur.
Bhujwalla
Z M
ZM
MR Oncology Section, Division of MR Research, Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. zaver@mri.jhu.edu
Artemov
D
D
Natarajan
K
K
Ackerstaff
E
E
Solaiyappan
M
M
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000556:secondary; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology; D003287:Contrast Media / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019786:Gadolinium DTPA / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009336:Necrosis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000418:Albumins; D003287:Contrast Media; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019786:Gadolinium DTPA