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Open Access Highly Accessed Research article

Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

Michael Samoszuk1*, Jenny Tan1 and Guillaume Chorn2

Author Affiliations

1 Pathology Department, University of California, Irvine, California, USA

2 Biology Department, Stanford University, Stanford, California, USA

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Breast Cancer Research 2005, 7:R274-R283  doi:10.1186/bcr995

Published: 28 January 2005

Abstract

Introduction

Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts.

Methods

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 α-smooth muscle actin.

Results

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.

Conclusion

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.

Keywords:
fibroblasts; metastatic; microarrays; myofibroblasts; serum