title: Matrigel alters the pathophysiology of orthotopic human breast adenocarcinoma xenografts with implications for nanomedicine evaluation.
abstract: Matrigel, a mouse sarcoma-derived basement membrane protein mixture, is frequently used to facilitate human tumor xenograft growth in rodents. Despite its known effects on tumor growth and metastasis, its impact on tumor pathophysiology and preclinical evaluation of nanomedicines in tumor xenografts has not been reported previously. Herein bilateral MDA435 tumors were established orthotopically with (Mat+) or without (Mat-) co-injection of Matrigel. Tumor perfusion, morphology and nanoparticle retention were evaluated. As compared to Mat- tumors, Mat+tumors exhibited enhanced vascular perfusion and lymphatic flow, greater blood vessel and lymphatic growth within the tumor core, and more deformation and collapse of lymphatics in tumor-associated lymph nodes. These changes were accompanied by reduced nanoparticle retention in Mat+tumors. The results suggest that Matrigel is not a passive medium for tumor growth, but rather significantly alters long-term tumor architecture. These findings have significant implications for the evaluation of therapeutic nanomedicine in xenograft mouse models.
  
  
  BACKGROUND
  Matrigel is utilized in facilitating human tumor xenograft growth in rodents. The authors demonstrate that Matrigel is not a passive medium for tumor growth; instead it significantly alters long-term tumor architecture, with major implications in the evaluation of therapeutic nanomedicine in xenograft mouse models.
authors: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
authors: Adam J
authors: AJ
authors: Shuhendler
authors: Preethy
authors: P
authors: Prasad
authors: Ping
authors: P
authors: Cai
authors: Kelvin K W
authors: KK
authors: Hui
authors: Jeffrey T
authors: JT
authors: Henderson
authors: Andrew M
authors: AM
authors: Rauth
authors: Xiao Yu
authors: XY
authors: Wu
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology*; D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D045744:Cell Line, Tumor; D003094:Collagen / Q000008:administration & dosage* / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D064593:Heterografts / Q000503:physiopathology*; D006801:Humans; D007797:Laminin / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011509:Proteoglycans / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen
keywords: Altered pathophysiology; Enhanced tumor perfusion; Lymphangiogenesis; Matrigel; Nanoparticle retention; Orthotopic breast adenocarcinoma xenografts