Implication of scatter/growth factors in tumor progression.
Several steps during cancer progression have been distinguished on the basis of anatomo-pathological observations and experimental data. The first step, which consists of the detachment of the cancer cells from the primary tumor prior to their migration, has received much attention. Several lines of evidence have indicated that inducer molecules of tumor cell dispersion are scatter factors which are similar or identical to some growth factors. Our studies have focused on the dispersing effect of growth factors, such as acidic FGF (aFGF) on a rat bladder carcinoma cell line. These studies demonstrated that specific extracellular matrix components might contribute to the scattering effect of soluble growth factors. Additionally, our results indicated that the dispersing action of aFGF is counterbalanced by its mitogenic effect, since these two functions of aFGF cannot be observed simultaneously for the same cell. Depending on its location in the cell collective, a given cell chooses to enter mitosis or to scatter in response to aFGF. The choice between the two responses is apparently driven by molecules belonging to the transducing pathways of aFGF signaling. Finally, our data indicated that aFGF-induced tumor cell scattering leads to increased in vitro invasiveness and in vivo metastasis. Interestingly, the presence of few aFGF-producing tumor cells in a population of non-producing cells dramatically enhances the growth rate and the metastatic properties of the whole tumor, suggesting that a low proportion of highly metastatic cells in a heterogeneous cell population might modify the behavior of the tumor mass.
Boyer
B
B
Laboratoire de Physiopathologie du Développement Ecole Normale Supérieure Paris, France.
Vallés
A M
AM
Jouanneau
J
J
Delouvée
A
A
Thiery
J P
JP
D000818:Animals; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D003896:Desmosomes / Q000187:drug effects; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000494:pharmacology*; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology*
D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D016220:Fibroblast Growth Factor 1; D000242:Cyclic AMP