[Molecular aspects of invasiveness and metastasis].
Tumor progression involves the emergence of cell variants with increased proliferative and invasive potentialities. The acquisition of the invasive and metastatic behavior is associated with modulation of cell-cell and cell-substrate interactions. Tumor cells have to dissociate from the primary tumor and migrate through the basal lamina and the surrounding stroma before reaching the vessels. An aberrant expression of some growth factors and their cognate receptors, may contribute to an increase malignancy of tumor cells. We have postulated than such growth factors could be involved in the early events of metastatic spreading by altering cell interactions within a tumor, including proliferation, scattering and migration of tumor cells. In the rat bladder carcinoma NBT-II cell experimental model, we have shown that FGF-1 is a multifunctional factor during tumor progression; FGF-1 acts as a mitogenic factor, a scatter factor, an angiogenic factor, an inducer of matrix degradating enzymes and a tumorigenic factor. NBT-II cells producing constitutively FGF-1 are more invasive, tumorigenic and metastatic than non-producing cells. However, we have shown that within a tumor, FGF-1 producing cells are not dominant in vivo but rather confer by a community effect an "en bloc" behavior to the whole cell collective. This effect could be established either directly by a paracrine mechanism or indirectly by other induced factors. We provide evidence for a novel concept in tumor biology: tumor progression may result from a community effect mediated by a growth/scatter factor produced by a minority of the carcinoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Jouanneau
J
J
Laboratoire de Physiopathologie du Développement, URA 1337 CNRS, ENS, Paris, France.
Bellusci
S
S
Moens
G
G
Thiery
J P
JP
D016220:Fibroblast Growth Factor 1 / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D016211:Transforming Growth Factor alpha / Q000502:physiology
D016211:Transforming Growth Factor alpha; D016220:Fibroblast Growth Factor 1; D017228:Hepatocyte Growth Factor