The community effect in FGF-1 mediated tumor progression of a rat bladder carcinoma does not involve a direct paracrine signaling

Abstract

A community e ect was found to occur between heterogeneous tumor cell populations leading to an overall increased tumorigenicity without a clonal dominance of the more tumorigenic clone. In the rat bladder carcinoma cell line NBT-II, this e ect appears mediated by the Fibroblast Growth Factor-1 (FGF-1) through either a direct or an indirect signaling pathway. Neovascularization induced by FGF-1 was found not to be responsible for the community e ect. The present study shows that the community e ect does not involve a direct FGF-1 signaling since tumor cells expressing a dominant-negative FGF receptor mutant were still responding to the highly tumorigenic FGF-1 expressing cells. Tumors arising from inoculates of the FGF-1 producing NBT-II cells mixed with non tumorigenic epithelial MDCK cells contain only the tumorigenic cells indicating that MDCK cells may exerce a helper e ect for the growth of the tumor not dependant on their own growth. Therefore the helper function of MDCK cells must be distinguished from a community e ect where the contribution of low tumorigenic cells not only provides an in vivo growth advantage to few highly tumorigenic cells but become themselves highly tumorigenic indicating that the community e ect may require cell-cell speci®c cooperativity independent from an helper e ect.

In vivo mechanisms by which tumors producing thrombospondin 1 bypass its inhibitory effects

“…Non-resistant tumor cells also favor the growth of TSP1-resistant ones: when TSP1 was turned on after 18 d in tumors, when cells had divided about 12 times and the heterogeneity of the cell population had thus increased, resistance developed more rapidly than when TSP1 was expressed starting on day 0. Multiple clonal variants would cooperate during tumor progression through "community" effects (Jouanneau et al 1999) involving secreted factors, cell-cell interactions, or both. Resistance to TSP1, as it results among others in an increased secretion of angiogenic factors, would be one of the mechanisms involved in these community effects.…”

Alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl- glycerophosphocholine induces invasion through episialin-mediated neutralization of E-cadherin in human mammary MCF-7 cellsin vitro

“…The fact that the episialin-negative cells are not refractory to ET-18-OMe can be due to the "community effect" described for mixed cell populations with one type of cell dominating the other via cell-cell interactions. 41 Indeed, in a mixture with a minority of MCF7/AZ and a majority of MCF7/6 cells, the MCF-7/AZ phenotype dominates and cells become adhesion-proficient (M. Bracke, personal communication).…”

Direct FGF receptor 1 activation through an anti-idiotypic strategy mimicks the biological activity of FGF-2 and inhibits the progression of the bladder carcinoma derived from NBT-II cells

“…The constitutive expression of FGF-1 or FGF-2 by these carcinoma cells generates cells that secrete the corresponding growth factor and that in vivo allow the growth of highly vascularized tumors as well in autocrine or nonautocrine NBT-II-expressing cells (Jouanneau et al, 1997;Billottet et al, 2002). However, a major difference in growth rate was observed: tumors developing NBT-II cells expressing FGF-2 grew like the control, whereas the growth rate of FGF-1-expressing cells was much faster (Jouanneau et al, 1997(Jouanneau et al, , 1999. Although constitutive expression of the high-affinity receptor FGFR-1 gave cells that have acquired the capacity to be activated by exogenous FGF-2, these cells induced tumors with growth properties similar to that of parental cells (Moscatelli, 1992); conversely, when they are engineered to constitutively express FGFR-1 and FGF-2, they behave like FGF-1-producing cells (Billottet et al, 2002).…”

“…Previously, we showed that tumors derived from FGF-1-transfected NBT-II cells grew faster than tumors obtained with control or FGF-2-transfected cells, irrespective of their angiogenic status (Jouanneau et al, 1997(Jouanneau et al, , 1999. Furthermore, NBT-II cellsengineered autocrine for FGF-2 became highly tumorigenic but present the same tumor vascularization (Billottet et al, 2002).…”