Influence of matrigel on biodistribution studies in cancer research.
Matrigel matrix is widely used for supporting tumour implantation. However, some tumour cells are unable to degrade matrigel matrix resulting in residual matrigel at the time point of the biodistribution study or therapy experiment. In vitro cell uptake of tumour affine compounds into tumour cells embedded in matrigel was compared with matrigel free tumour cells. Matrigel accumulation exceeded cellular uptake of the tumour affine peptides. This suggests that matrigel might have an influence on the acquired biodistribution data when it is still present at the time point of the study. A quantitation of residual matrigel in tumour explants fourteen days after tumour implantation with a matrigel-tumour cell mixture showed that the overall matrigel content in the case of MCF-7 and AR42J tumours was about 23%. In order to evaluate the extent of accumulation of compounds in matrigel, nude mice bearing either tumours, tumour-matrigel-mixtures or matrigel alone received intravenous injections of fluorophor tagged tumour specific peptides. Fluorescence microscopy of cryosectioned matrigel, matrigel-tumour mixtures and tumour explants showed that the labelled compounds were matrigel associated and tumour cell associated with a higher fluorescence intensity in matrigel. In summary, matrigel matrix can influence biodistribution studies. It leads to believe in a higher tumour accumulation. Therefore, either a number of control experiments or the separation of matrigel from the tumour is necessary in order to obtain correct biodistribution data.
Wolf
Markus
M
Department of Radiopharmaceutical Chemistry, German Cancer Research Centre, Heidelberg, Germany. elodeadensa@aol.com
D000818:Animals; D016477:Artifacts; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007797:Laminin / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution
D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; D010455:Peptides; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen