{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:35:09Z","timestamp":1769042109316,"version":"3.49.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T00:00:00Z","timestamp":1106870400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T00:00:00Z","timestamp":1106870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>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 <jats:italic>in vitro<\/jats:italic> model of the interaction between small numbers of human breast cancer cells and human fibroblasts.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>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 <jats:italic>in vivo<\/jats:italic> relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing \u03b1-smooth muscle actin.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Clonogenic growth of human breast cancer cells obtained directly from <jats:italic>in situ<\/jats:italic> 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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells <jats:italic>in vitro<\/jats:italic> 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.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/bcr995","type":"journal-article","created":{"date-parts":[[2005,1,29]],"date-time":"2005-01-29T08:05:56Z","timestamp":1106985956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts"],"prefix":"10.1186","volume":"7","author":[{"given":"Michael","family":"Samoszuk","sequence":"first","affiliation":[]},{"given":"Jenny","family":"Tan","sequence":"additional","affiliation":[]},{"given":"Guillaume","family":"Chorn","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2005,1,28]]},"reference":[{"key":"993_CR1","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1006\/excr.2000.5133","volume":"264","author":"B Elenbaas","year":"2001","unstructured":"Elenbaas B, Weinberg RA: Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. 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