Invasiveness of human pleural mesothelioma cells is influenced in vitro by the three-dimensional structure of the ECM and its composition

The grade of malignancy of a neoplasm is influenced by the invasive and metastatic potential of the tumor cells. The extracellular matrix of tissues is known to interact with many aspects of the biological behavior of tumor cells, such as differentiation and invasiveness. Therefore we studied the influence of the extracellular matrix on the morphology and invasiveness of the human biphasic pleural mesothelioma cell line MSTO-211H in vitro. The major components of the two strata encountered by a pleural mesothelioma cell leaving the epithelial community were mimicked by plating cells either on collagen I, the major component of the underlying stratum fibrosum, being encountered by cells under pathological conditions or on reconstituted basement membrane (Matrigel®) in order to simulate the basement membrane of the stratum serosum of the mesothelium, which is the matrix cells have contact to under physiological conditions. Growth on collagen I leads to cell separation and invasion into the matrix, whereas growth of MSTO-211H cells on Matrigel® results in the formation of a huge and dense network of cells extending throughout the whole plating area. The morphology of cell contacts between the two populations varies impressively. While cells on collagen I hardly find to each other in groups, and if so, with a broad intercellular cleft, Matrigel® induces the tight approach of membranes of neighbouring cells with formation of syncytium-like structures. Administration of the main ECM components laminin and collagen IV alone and together in equimolar concentrations as present in Matrigel®, does not result in any morphological changes when compared to cells growing on plastic substrates or on collagen I. Therefore, collagen I increases cell separation and invasiveness whereas an intact basement membrane seems to prevent the cells from separating and spreading, thus lowering their invasive potential.