Breast fibroblasts modulate epithelial cell proliferation in three-dimensional in vitro co-culture

Abstract

Background Stromal fibroblasts associated with in situ and invasive breast carcinoma differ phenotypically from fibroblasts associated with normal breast epithelium, and these alterations in carcinoma-associated fibroblasts (CAF) may promote breast carcinogenesis and cancer progression. A better understanding of the changes that occur in fibroblasts during carcinogenesis and their influence on epithelial cell growth and behavior could lead to novel strategies for the prevention and treatment of breast cancer. To this end, the effect of CAF and normal breastassociated fibroblasts (NAF) on the growth of epithelial cells representative of pre-neoplastic breast disease was assessed.

Artemin is oncogenic for human mammary carcinoma cells

“…It has been widely recognized that the tumor microenvironment plays a major role in dictating tumor behavior and progression, as well as response to therapy (Lubaroff et al, 1980;Chung, 1993;Pettaway et al, 1996;Singh et al, 2007). Indeed, mammary stromal fibroblasts have been shown both in vitro and in vivo to modulate mammary carcinoma cell proliferation (Brouty-Boye and Raux, 1993;Sadlonova et al, 2005). Therefore, the ARTN stimulated increase in BrdU-positive cells in vivo, but not in vitro, is indicative that artemin also possesses stromal or paracrine interactions in vivo.…”

Microenvironmental regulation of cancer development

“…This was first and most dramatically demonstrated by the lack of tumor development in chick embryos infected with the Rous sarcoma virus expressing a potent oncogene [20]. Normal myoepithelial cells have been shown able to suppress the growth, invasion, and angiogenesis of multiple different breast cancer cell types [21][22][23], whereas the effects of normal fibroblasts are more dependent on the ratio of stromal and epithelial cells and the degree of malignancy of the tumor cells [24].…”

Exosomes: recruits for tumour surveillance?

“…Both NAFs and CAFS could inhibit the growth of the low grade MCF10A cells but only the NAFs could block the growth of the high grade neoplastic cells MCF10AT. The authors speculate that NAFs are more effective in tumour suppression and this suppressive ability may be lost or reduced as epithelial lesions gradually progress from hyperplasia to invasive cancer, and accordingly NAF are activated to transform into CAFs (23). In a second study using the same two cell lines but this time grafted in a mouse, Sadlonova et al implanted the tumours with NAFs and compared their effect on low and high grade lesions.…”