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Induction of matrix metalloproteinases MMP-1 and MMP-2 by co-culture of breast cancer cells and bone marrow fibroblasts

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Abstract

Two invasive breast cancer cell lines (MDA-MB-231 and BT-549) were found to be more adherent and have greater migratory capacity on bone marrow fibroblasts than three non-invasive cell lines (MCF-7, T47D and BT-483). Antibodies to the adhesion molecules CD44, E-cadherin, ICAM-1, and integrin chains α2, α3, α4, α5, α6, αv, α1, α3 and α7 failed to inhibit breast cancer cell migration through bone marrow fibroblasts. Inhibitors of matrix metalloproteases, 1, 10-phenanthroline, Ro-9790, TIMP-1 and TIMP-2 were able to attenuate the migration of MDA-MB-231 cells through bone marrow fibroblast monolayers suggesting a role for these enzymes in the migration of breast cancer cells through bone marrow adherent layers. Co-culture of MDA-MB-231 cells and bone marrow fibroblasts resulted in augmentation of the levels of the matrix metalloproteases MMP-1 and MMP-2 in culture supernatants. Soluble factors produced by bone marrow fibroblasts were responsible for the increase in MMP-1 levels. However, maximal MMP-2 production was dependent on direct contract between the breast cancer cells and the bone marrow fibroblasts. Modulation of MMP production by cell–cell contact or soluble factors suggests a mechanism by which breast cancer cells can enhance their ability to invade the bone marrow microenvironment.

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Authors
  1. Sonia Saad
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  2. Linda J Bendall
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  3. Alexander James
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  4. David J Gottlieb
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  5. Kenneth F Bradstock
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Saad, S., Bendall, L.J., James, A. et al. Induction of matrix metalloproteinases MMP-1 and MMP-2 by co-culture of breast cancer cells and bone marrow fibroblasts. Breast Cancer Res Treat 63, 105–115 (2000). https://doi.org/10.1023/A:1006437530169

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