Abstract
BackgroundMetastasis of breast cancer displays site-specificity towards bone. Recently, studies have emerged indicating that primary tumors may remotely influence creation of a pre-metastatic niche. In this study, we used human fetal osteoblastic cells and MDA-MET, a metastatic and preferentially bone homing derivative of the breast cancer cell line MDA-MB-231. We examined 1) whether secreted factors from MDA-MET cells increase generation of chemoattractants by human foetal osteoblastic cells 2) whether MDA-MET cells were responsive to these chemoattractants and 3) the identity of these chemoattractants.MethodsHuman foetal osteoblastic cells were treated with conditioned medium of MDA-MET cells for 24 hours and then washed with phosphate-buffered saline. Serum-free replacement medium was conditioned by treated hFOB cells for 18 hours, before its use in in vitro quantification of MDA-MET migration. We also quantified collagen levels and collagenase activity in conditioned medium from human foetal osteoblastic cells.ResultsConditioned medium from human foetal osteoblastic cells that had been treated with MDA-MET-conditioned medium attracted more MDA-MET cells than hFOB cells pre-exposed to their own medium. This conditioned medium had increased collagenase activity. The addition of bacterial collagenase removed the ability of conditioned medium from human foetal osteoblastic cells to attract MDA-MET cells.ConclusionsOur data suggest that an increase in collagenase activity in osteoblastic cells induced by their exposure to breast cancer cell–secreted factors may increase their ability to attract breast cancer cells.
Highlights
Metastasis of breast cancer displays site-specificity towards bone
Migration assays revealed that MDA-MET cells migrated towards hFOBCM [METCM] to a greater degree than towards hFOBCM [hFOBCM](conditioned medium from human fetal osteoblastic cells (hFOB) cells which had been previously exposed to conditioned medium from hFOB cells), hFOBCM [HTERTCM] or unconditioned medium (Fig. 1 Left Panel)
When human bone marrow endothelial cells (HBMEC) cells were used instead of hFOB, there was no difference among groups in the number of MDA-MET cells migrating towards HBMECconditioned medium, i.e. an equal number of MDAMET cells migrated towards HBMECCM [HBMECCM], HBMECCM[METCM] and HBMECCM[HTERTCM] respectively (Fig. 1 Right Panel)
Summary
Metastasis of breast cancer displays site-specificity towards bone. Recently, studies have emerged indicating that primary tumors may remotely influence creation of a pre-metastatic niche. We used human fetal osteoblastic cells and MDA-MET, a metastatic and preferentially bone homing derivative of the breast cancer cell line MDA-MB-231. Approaches to cancer treatment have limited success when a tumor has metastasized The reason for this is not currently known. In 2005, Kaplan et al produced in vivo evidence that secreted factors from a primary tumor could modify its metastatic target in a pro-metastatic manner [1]. They summarized these changes by coining the term the “premetastatic” niche; which they predicted would appear in a tissue known to be favored by a given tumor for metastasis.
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