Comparison of IgG diffusion and extracellular matrix composition in rhabdomyosarcomas grown in mice versus in vitro as spheroids reveals the role of host stromal cells

Br J Cancer. 2002 May 20;86(10):1639-44. doi: 10.1038/sj.bjc.6600270.

Abstract

The tumour extracellular matrix acts as a barrier to the delivery of therapeutic agents. To test the hypothesis that extracellular matrix composition governs the penetration rate of macromolecules in tumour tissue, we measured the diffusion coefficient of nonspecific IgG in three rhabdomyosarcoma subclones growing as multicellular spheroids in vitro or as subcutaneous tumours in dorsal windows in vivo. In subcutaneous tumours, the diffusion coefficient decreased with increasing content of collagen and sulphated glycosaminoglycans. When grown as multicellular spheroids, no differences in either extracellular matrix composition or diffusion coefficient were found. Comparison of in vitro vs in vivo results suggests an over-riding role of host stromal cells in extracellular matrix production subjected to modulation by tumour cells. Penetration of therapeutic macromolecules through tumour extracellular matrix might thus be largely determined by the host organ. Hence, caution must be exercised in extrapolating drug penetrability from spheroids and multilayer cellular sandwiches consisting of only tumour cells to tumours in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Culture Techniques / methods
  • Clone Cells / chemistry
  • Clone Cells / cytology
  • Clone Cells / transplantation
  • Collagen / analysis
  • Diffusion
  • Extracellular Matrix / chemistry*
  • Glycosaminoglycans / analysis
  • Hyaluronic Acid / analysis
  • Immunoglobulin G / metabolism*
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Rats
  • Rhabdomyosarcoma / pathology*
  • Skin Window Technique
  • Spheroids, Cellular / chemistry
  • Spheroids, Cellular / cytology*
  • Spheroids, Cellular / transplantation
  • Stromal Cells / physiology*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / transplantation

Substances

  • Glycosaminoglycans
  • Immunoglobulin G
  • Hyaluronic Acid
  • Collagen