Extracellular Matrix Components Regulate Bone Sialoprotein Expression in MDA-MB-231 Breast Cancer Cells.

Florian Keller,Franziska Clauder,Rüdiger Rudolf,Mathias Hafner,Roman Bruch

doi:10.3390/cells10061304

Florian Keller, Franziska Clauder + Show 3 more

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https://doi.org/10.3390/cells10061304

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Abstract

Bone sialoprotein (BSP) has become a target in breast cancer research as it is associated with tumor progression and metastasis. The mechanisms underlying the regulation of BSP expression have been largely elusive. Given that BSP is involved in the homing of cancer cells in bone metastatic niches, we addressed regulatory effects of proteolytic cleavage and extracellular matrix components on BSP expression and distribution in cell culture models. Therefore, MDA-MB-231 human breast cancer cells were kept in 2D and 3D spheroid cultures and exposed to basement membrane extract in the presence or absence of matrix metalloproteinase 9 or the non-polar protease, dispase. Confocal imaging of immunofluorescence samples stained with different antibodies against human BSP demonstrated a strong inducing effect of basement membrane extract on anti-BSP immunofluorescence. Similarly, protease incubation led to acute upregulation of anti-BSP immunofluorescence signals, which was blocked by cycloheximide, suggesting de novo formation of BSP. In summary, our data show that extracellular matrix components play an important function in regulating BSP expression and hint at mechanisms for the formation of bone-associated metastasis in breast cancer that might involve local control of BSP levels by extracellular matrix degradation and release of growth factors.

Highlights

Breast cancer is one of the most lethal illnesses for women and the most common type of malignancy besides skin cancer
Some evidence suggests a role of growth factors such as transforming growth factor beta (TGFβ), vascular endothelial growth factor (VEGF) and interleukins, such as interleukin-6 (IL-6), in the underlying remodeling processes at osteolytic metastatic sites [5]
Investigations in nude mice indicate that homing and niche formation of breast cancer cells are independent of estrogen receptor status [6] and the mode of action might be transferable to different breast cancer types

Summary

Introduction

Breast cancer is one of the most lethal illnesses for women and the most common type of malignancy besides skin cancer. Niche formation for metastatic apposition is a common mechanism [3]. Some evidence suggests a role of growth factors such as transforming growth factor beta (TGFβ), vascular endothelial growth factor (VEGF) and interleukins, such as interleukin-6 (IL-6), in the underlying remodeling processes at osteolytic metastatic sites [5]. Investigations in nude mice indicate that homing and niche formation of breast cancer cells are independent of estrogen receptor status [6] and the mode of action might be transferable to different breast cancer types. Breast cancer lesions are located within trabecular bone regions that are rich in osteoblasts and micro-vessels and may overlap with the hematopoietic stem cell niche [7]. Trabecular bone has the same lamellar structure as compact bone [8], slight differences in remodeling processes of these two bone types may give a hint why trabecular bone is preferred for metastasis

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