Adipocyte differentiation influences the proliferation and migration of normal and tumoral breast epithelial cells

PISTONE CREYDT V; SACCA PA; TESONE AJ; VIDAL L; CALVO JC

MOLECULAR MEDICINE REPORTS

SPANDIDOS PUBL LTD

Año: 2010 vol. 3 p. 433 - 439

1791-2997

Abstract.  Stromal  tissue  regulates  the  development  and differentiation of breast epithelial cells, with adipocytes being the main stromal cell type. The aim of the present study was to evaluate the effect of adipocyte differentiation on proliferation and migration, as well as to assess the activity of heparanase and metalloproteinase-9 (MMP-9), in normal (nMuMG) and tumoral  (lM3)  murine  breast  epithelial  cells.  nMuMG  and lM3  cells  were  grown  on  irradiated  3T3-l1  cells  (stromal support,  SS)  at  various  degrees  of  differentiation  [preadipo-cytes  (prea),  poorly  differentiated  adipocytes  (pda)  and mature adipocytes (Ma)] and/or were incubated in the pres-ence of conditioned medium (cM) derived from each of these three  types  of  differentiated  cells.  cells  grown  on  a  plastic support or in fresh medium served as the controls. cell prolif-eration was measured with a commercial colorimetric kit, and the  motility  of  the  epithelial  cells  was  evaluated  by  means of  a  wound-healing  assay.  Heparanase  activity  was  assessed by  quantifying  heparin  degradation,  and  the  expression  of MMP-9  was  determined  using  Western  blotting.  The  results indicate that cell proliferation was increased after 24 and 48 h in the nMuMG and lM3 cells grown on prea, pda and Ma SS.  in  the  nMuMG  cells  cultured  on  SS  in  the  presence  of all three types of cM, proliferation was enhanced. lM3 cell migration was increased in the presence of all three types of cM and in cells grown on prea SS. Heparanase activity was increased in the nMuMG cells incubated with all three types of cM, and in the lM3 cells incubated with the cM from pda and  Ma.  Both  the  nMuMG  and  lM3  cell  lines  presented basal expression of MMP-9; however, a significant increase in MMP-9 expression was observed in the lM3 cells incubated with each of the three types of cM. in conclusion, adipocyte differentiation influences normal and tumoral breast epithelial cell  proliferation  and  migration.  Heparanase  and  MMP-9 appear  to  be  involved  in  this  regulation.  The  experimental model presented in this study is in keeping with the charac-teristics of the physiological environment of breast epithelial cells, in terms of both the soluble and insoluble factors present and the stromal structure per se.