Am. J. Respir. Cell Mol. Biol.,
Volume 21, Number 2, August, 1999 200-208
Three-Dimensional In Vitro Cocultivation of Lung Carcinoma Cells with
Human Bronchial Organ Culture as a Model for Bronchial Carcinoma
Salah-Eddin
Al-Batran,
Sabrina T.
Astner,
Merlind
Supthut,
Fernando
Gamarra,
Kathrin
Brueckner,
Ulrich
Welsch,
Ruth
Knuechel,
and
Rudolf M.
Huber
Department of Medicine, Klinikum Innenstadt; Institute of Anatomy, Ludwig-Maximilians-University, Munich; and
Department of Pathology, University of Regensburg, Regensburg, Germany
We describe the development of a three-dimensional in vitro organ culture model for bronchial carcinoma
using bronchial mucosa organ cultures and three different human non-small cell lung cancer cell lines.
During precultivation, bronchial fragments obtained as biopsies during routine bronchoscopy had regenerated a complete epithelial covering with a well-preserved organotypic architecture around a nucleus consisting of connective tissue. To create cocultures, different types of confrontation between tumor cells and
organ cultures were applied. Histologic light microscopy and scanning electron microscopy were used in
analysis. When tumor cells were confronted with completely epithelialized organ cultures, they showed a
low incidence of attachment. When organ cultures were wounded before confrontation, tumor cells always
attached to the wounded side and showed a progressive invasion into the stromal tissue. Measurements of
the penetration depth of tumor cells into the organ cultures after different incubation times permitted the
quantitative evaluation of invasion. Histologic studies revealed well-differentiated normal epithelium in
spite of long culture periods. Histologic features of the tumors were those of an invasive undifferentiated
carcinoma and showed marked similarities to the situation in vivo. The coculture model permits internal
controls because it contains both normal human epithelium and human tumor cells in the same organotypic
culture. Therefore it offers opportunities for various in vitro investigations on therapeutic and diagnostic modalities of lung cancer, as indicated in this paper by an example of photodynamic procedures with
5-aminolevulinic acid.
