%0 Journal Article
%T Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts
%A Michael Samoszuk
%A Jenny Tan
%A Guillaume Chorn
%J Breast Cancer Research
%D 2005
%I BioMed Central
%R 10.1186/bcr995
%X We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing ¦Á-smooth muscle actin.Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells.Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers.There is now increasing evidence that stromal cells play a pivotal role in promoting the growth of most carcinomas, including breast cancer [1-4]. The myofibroblast is the predominant type of stromal cell found in most carcinomas [1,5,6]. Myofibroblasts are defined by their characteristic expression of ¦Á-smooth muscle actin as well as certain other markers such as vimentin and desmin [1]. Tumor-associated myofibroblasts are believed to originate from normal fibroblasts and are similar or identical to the myofibroblasts found in healing wounds [1]. They are largely responsible for the desmoplasia that is char
%K fibroblasts
%K metastatic
%K microarrays
%K myofibroblasts
%K serum
%U http://breast-cancer-research.com/content/7/3/R274