Influence of tumor derived fibroblasts and 1,25-dihydroxyvitamin D3 on growth of breast cancer cell lines

Abstract

Fibroblasts are known to be present in variable amounts in human breast adenocarcinoma tissue. In order to investigate if they influence in some way the proliferation rate of the carcinoma cells, we developed a coculture model in which cells of well characterized breast epithelial cell lines were seeded and grown in microchamber slides along with fibroblasts derived from breast tumor biopsies. As representatives of hormone dependent and independent tumor cells, we used MCF-7 and BT-20 cell lines. A third line, NPM-21T, derived from non proliferating mastopathy cells immortalized by SV-40 T DNA transfection, was representative of non tumor epithelial cells. The proliferation rate of the adenocarcinoma and epithelial cells was assessed by measurement of the BrdU labeling index, the cells being identified by specific beta-actin immunostaining. It was found that the proliferation of the adenocarcinoma cells was significantly increased in the presence of fibroblasts, while that of immortalized cells was not. Moreover, 1,25(OH)2D3, which was known to be a negative regulator of carcinoma cell growth, was found to be able also to blunt the overgrowth in the presence of fibroblasts. The absence of response of NPM-21T cells to the presence of fibroblasts suggests that the tumor cells could be the origin of their own overgrowth, through an indirect mechanism mediated by the fibroblasts. The factors which are involved and the 1,25(OH)2D3 mechanism of action are not yet identified.

Positive regulation of normal and tumoral mammary epithelial cell proliferation by fibroblasts in coculture

“…Fibroblasts were also able to stimulate BT-20 cell line growth that was significantly higher than the proliferative response observed for the MCF-7 cell line. Growth stimulation of BT-20 ceils by fibroblasts derived from breast tumor biopsies has also been observed in direct cocuhure by Lefebvre et al (1995). However, in contrast to our results, the level of the proliferative response was similar in BT-20 and MCF-7 cell lines.…”

“…Conversely, Hofland et al (1995) described recently growth stimulation of MCF-7 carcinoma cells by normal human foreskin fibroblasts when cocultured in permeable tissue-culture systems. Lefebvre et al (1995), using a monolayer coculture system, demonstrated that fibroblasts derived from breast tumor biopsies were able to stimulate the proliferation of carcinoma cell lines. Finally, van Roozendaal et al (1992van Roozendaal et al ( , 1996 demonstrated that conditioned serum-free media produced by breast fibroblasts in primary culture were able to stimulate the proliferation of a variety of breast carcinoma cell lines.…”

The fibrotic focus in advanced colorectal carcinoma: a hitherto unrecognized histological predictor for liver metastasis

“…c : & t b l . growth factors produced by stromal fibroblasts have been shown to stimulate the growth of breast cancer cells [17] and the invasiveness of scirrhous gastric cancer cells [14]. Many growth factors also have angiogenetic effects in cancer tissue [27].…”

Inhibition of the invasion capacity of carcinoma cells by WX‐UK1, a novel synthetic inhibitor of the urokinase‐type plasminogen activator system

“…The role of fibroblasts in tumor proliferation is unclear. Tumor-derived fibroblasts have been described as stimulating tumor cell progression of different breast cancer cell lines, 33,34 whereas fibroblasts from healthy breast tissue inhibited tumor cell growth of MCF-7 cells. 35 However, there is abundant evidence that host tissue cells such as fibroblasts do actively participate in malignant invasion upon the production of soluble factors, different cytokines, proteolytic enzymes and/or components of the extracellular matrix.…”