Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting.
Breast cancers can express different types of peptide receptors such as somatostatin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and NPY(Y(1)) receptors. The aim of this in vitro study was to evaluate which is the most appropriate peptide receptor or peptide receptor combination for in vivo diagnostic and therapeutic targeting of breast cancers. Seventy-seven primary breast cancers and 15 breast cancer lymph node metastases were investigated in vitro for their expression of somatostatin, VPAC(1), GRP and NPY(Y(1)) receptors using in vitro receptor autoradiography on successive tissue sections with (125)I-[Tyr(3)]-octreotide, (125)I-VIP, (125)I-[Tyr(4)]-bombesin and (125)I-[Leu(31),Pro(34)]-PYY respectively. This study identified two groups of tumours: a group of 68 tumours (88%) with at least one receptor expressed at high density (>2,000 dpm/mg tissue) that may provide a strong predictive value for successful in vivo targeting, and a group of nine tumours (12%) with no receptors or only a low density of them (<2,000 dpm/mg tissue). In the group with high receptor density, 50 of the 68 tumours (74%) expressed GRP receptors, 45 (66%) expressed NPY(Y(1)) receptors, 25 (37%) expressed VPAC(1) receptors and 14 (21%) expressed somatostatin receptors. Mean density was 9,819+/-530 dpm/mg tissue for GRP receptors, 9,135+/-579 dpm/mg for NPY(Y(1)) receptors, 4,337+/-528 dpm/mg for somatostatin receptors and 3,437+/-306 dpm/mg for VPAC(1) receptors. It is of note that tumours expressing NPY(Y(1)) or GRP receptors, or both, were found in 63/68 (93%) cases. Lymph node metastases showed a similar receptor profile to the corresponding primary tumour. This in vitro study strongly suggests that the combination of radiolabelled GRP and Y(1) analogues should allow targeting of breast carcinomas and their lymph node metastases for in vivo peptide receptor scintigraphy and radiotherapy.
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, PO Box 62, Murtenstrasse 31, Switzerland. reubi@patho.unibe.ch
Claude
C
Reubi
Mathias
M
Gugger
Beatrice
B
Waser
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D001345:Autoradiography; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D018276:Carcinoma, Medullary / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008207:Lymphatic Metastasis; D018004:Receptors, Bombesin / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism; D017481:Receptors, Somatostatin; D018005:Receptors, Vasoactive Intestinal Peptide; D014018:Tissue Distribution
D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D018004:Receptors, Bombesin; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y; D018000:Receptors, Peptide; D017481:Receptors, Somatostatin; D018005:Receptors, Vasoactive Intestinal Peptide; C097212:neuropeptide Y-Y1 receptor