Investigation of mammary epithelial cell-bone marrow stroma interactions using primary human cell culture as a model of metastasis

Abstract

A model has been established using primary human cell culture to study the cell biology of breast cancer metastasis to bone marrow. Mammary epithelia were obtained in single cell suspension from tumour (macroscopically involved), benign (macroscopically uninvolved) and normal (reduction mammoplasty) breast tissue as well as from locally involved lymph nodes. Stromal layers were generated from long‐term cultures of human bone marrow or from mammary fibroblasts derived from normal or malignant tissue. The interaction between epithelia and stroma has been studied in terms of adhesion of the epithelia to the stroma and their subsequent growth in co‐culture. Our results show that when assayed up to 9 hr after plating, epithelial cells from malignant tissue (14 primary tumours and 9 metastases in lymph nodes) displayed a significant preference for adhesion to bone marrow stroma compared with mammary fibroblasts. In contrast, epithelial cells from 4 normal and 2 of 4 benign samples showed no significant preferential adherence. Subsequent co‐culture of mammary epithelia with each of the 3 stromal layers revealed that under serum‐free, in vitro conditions, bone marrow stromal layers did not provide an advantageous environment for colony growth, in contrast to their ability to provide a preferential substratum for adhesion. Int. J. Cancer 73:690–696, 1997. © 1997 Wiley‐Liss, Inc.

Tumor STAT1 Transcription Factor Activity Enhances Breast Tumor Growth and Immune Suppression Mediated by Myeloid-derived Suppressor Cells

“…Several lines of evidence implicate tumor-derived factors accumulating over time in promoting tumor tolerance and immune suppression, thereby driving aggressive cancer progression (6,7). In order to investigate tumor-derived factors that promote breast cancer progression, we have developed a syngeneic orthotopic transplantation mouse model of breast cancer progression (8). In this model, the TM40D-MB tumor cells, originally derived from the TM40D tumor cells, developed mammary tumors that are more aggressive and metastatic when they were implanted to the mammary fat pads of BALB/c mice.…”

Breast Cancer Metastasis: Advances Through the Use of In Vitro Co-Culture Model Systems

“…The epithelial cells from normal or benign breast showed no preference for any of the stromal substrates. Interestingly, although breast tumour epithelial cells adhered preferentially to bone cells, this stromal environment did not provide a preferential growth platform (Brooks, Bundred et al 1997). A similar study was carried out in Marseilles, France to determine the effect of stromal and epithelial cells from normal and tumorous breast tissue on growth of breast cancer cell lines.…”

“…These cells were first observed by Friedenstein in 1976 (Friedenstein, Gorskaja et al 1976) and have come to be defined as non-hematopoietic cells derived from bone stroma that are spindle-shaped and can be separated from other bone stromal cells by their tendency to adhere to plastic tissue culture plates. They have the stem cell characteristics of being able to differentiate into multiple cell lineages such as osteoblasts, chondrocytes, adipocytes and myoblasts and they express a consistent set of marker proteins on their surface (Brooks, Bundred et al 1997;Pittenger, Mackay et al 1999). Mesenchymal stem cells have been used in a number of laboratories in co-culture experiments with breast cancer cell lines or primary tumour cells and have been found to influence breast cancer cell adhesion, morphology, gene expression, proliferative capacity and growth characteristics (Brooks, Bundred et al 1997;Hombauer and Minguell 2000;Fierro, Sierralta et al 2004;Oh, Moharita et al 2004).…”

“…They have the stem cell characteristics of being able to differentiate into multiple cell lineages such as osteoblasts, chondrocytes, adipocytes and myoblasts and they express a consistent set of marker proteins on their surface (Brooks, Bundred et al 1997;Pittenger, Mackay et al 1999). Mesenchymal stem cells have been used in a number of laboratories in co-culture experiments with breast cancer cell lines or primary tumour cells and have been found to influence breast cancer cell adhesion, morphology, gene expression, proliferative capacity and growth characteristics (Brooks, Bundred et al 1997;Hombauer and Minguell 2000;Fierro, Sierralta et al 2004;Oh, Moharita et al 2004). They have been shown in vivo to be able to migrate to sites of tissue damage and to primary tumour sites, and to modify the ability of breast cancer tumours to metastasize to other organs, making them potentially interesting vehicles for cell-based anti-tumour agents (Ferrari, Cusella-De Angelis et al 1998;Hall, Dembinski et al 2007;Rhodes and Burow 2010).…”

Primary Human Mammary Epithelial Cells Endocytose HIV-1 and Facilitate Viral Infection of CD4 + T Lymphocytes

“…Milk is a very cellular fluid throughout the lactation period, with more than 10 6 leukocytes/ml in the colostrum (5, 26), followed by a decline over time to approximately 10 5 to 10 4 leukocytes/ml in mature milk (9,15,16,26). To reach the milk, lymphocytes and monocyte/macrophage populations must traffic paracellularly or transcellularly through a normally impermeable MEC monolayer on their way into the milk duct.…”