PMID- 20332440
OWN - NLM
STAT- MEDLINE
DCOM- 20100504
LR  - 20161125
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 30
IP  - 2
DP  - 2010 Feb
TI  - Effect of collagenase and hyaluronidase on free and anomalous diffusion in 
      multicellular spheroids and xenografts.
PG  - 359-68
AB  - BACKGROUND: A critical step in the delivery of nanomedicines to tumour cells is 
      transporting these particles through the extracellular matrix. Tumour-specific 
      anticancer agents, such as encapsulated drugs, proteins, and genes, show low 
      uptake in tumour tissue. It is not clear whether the collagen network or the 
      glycosaminoglycan gel plays the most important role in limiting the interstitial 
      transport of macromolecules. Therefore, we measured the effect of the collagen- 
      and hyaluronan-degrading enzymes, collagenase and hyaluronidase, on interstitial 
      diffusion. MATERIALS AND METHODS: Human osteosarcomas were grown as multicellular 
      spheroids and xenografts in dorsal skinfold window chambers. Diffusion of 
      fluorescein isothiocyanate (FITC)-dextran molecules was measured by fluorescence 
      recovery after photobleaching based on two-photon scanning laser excitation. 
      RESULTS: Collagenase, hyaluronidase, and relaxin increased the diffusion 
      coefficient of the 2-MDa FITC-dextrans in the spheroids, but 150-kDa FITC-dextran 
      diffusion was not affected by the enzymatic treatment. In tumour tissue in vivo, 
      collagenase and hyaluronidase increased the diffusion of the 150-kDa 
      FITC-dextrans. In xenografts, anomalous diffusion occurred, whereas only free 
      diffusion was seen in spheroids. CONCLUSION: The results indicate that the 
      collagen network has a greater impact on the interstitial diffusion of 
      macromolecules in tumour tissue than the hyaluronan gel.
FAU - Eikenes, Live
AU  - Eikenes L
AD  - Department of Physics, Norwegian University of Science and Technology, 
      Hogskoleringen 5, 7491 Trondheim, Norway.
FAU - Tufto, Ingunn
AU  - Tufto I
FAU - Schnell, Edrun A
AU  - Schnell EA
FAU - Bjorkoy, Astrid
AU  - Bjorkoy A
FAU - De Lange Davies, Catharina
AU  - De Lange Davies C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Dextrans)
RN  - 0 (fluorescein isothiocyanate dextran)
RN  - EC 3.2.1.35 (Hyaluronoglucosaminidase)
RN  - EC 3.4.24.- (Collagenases)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/enzymology/*pathology
MH  - Cell Line, Tumor
MH  - Collagenases/*metabolism
MH  - Dextrans
MH  - *Diffusion
MH  - Female
MH  - Fluorescein-5-isothiocyanate/analogs & derivatives
MH  - Fluorescence Recovery After Photobleaching
MH  - Humans
MH  - Hyaluronoglucosaminidase/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Microscopy, Fluorescence, Multiphoton
MH  - Models, Theoretical
MH  - Osteosarcoma/enzymology/*pathology
MH  - Spheroids, Cellular/enzymology/*pathology
MH  - Xenograft Model Antitumor Assays
EDAT- 2010/03/25 06:00
MHDA- 2010/05/05 06:00
CRDT- 2010/03/25 06:00
PHST- 2010/03/25 06:00 [entrez]
PHST- 2010/03/25 06:00 [pubmed]
PHST- 2010/05/05 06:00 [medline]
AID - 30/2/359 [pii]
PST - ppublish
SO  - Anticancer Res. 2010 Feb;30(2):359-68.